The need to treat mild hypertension. Misinterpretation of results from the Australian trial.

Despite the clear-cut result of the Australian Therapeutic Trial in Mild Hypertension, which demonstrated prospectively the benefit of treatment of diastolic blood pressure in the range of 95 to 109 mm Hg, a retrospective analysis that classified subjects by the average diastolic pressure level attained during the trial purported to show an absence of treatment benefit at lower average diastolic pressures and a negative treatment effect at higher levels. However, the method of classification by average attained diastolic pressure introduced substantial selection bias, invalidating the retrospective analysis and rendering as spurious both the deleterious treatment effect and its lack of efficacy at lower diastolic levels.

Dietary therapy slows the return of hypertension after stopping prolonged medication.

This study asks whether prolonged antihypertensive therapy will "cure" a substantial percent of rigorously treated hypertensive patients and whether nutritional change will add an antihypertensive effect and reduce the relapse rate. Of 584 eligible patients normotensive while receiving therapy, 496 were randomized into control and discontinued-medication groups with and without dietary intervention. At 56 weeks, 50% of those who were no longer receiving medication remained normotensive by study criteria. Randomization either to weight-loss group (mean loss of 4.5 kg [10 lb]) or to sodium-restriction group (mean reduction of 40 mEq/day) increased the likelihood of remaining without drug therapy, with an adjusted odds ratio of 2.17 for the sodium group and 3.43 for the weight group. Highest success rates were in the nonoverweight mild hypertensives with sodium restriction (78%) and the overweight mild hypertensives who were reducing their weight (72%). These data demonstrate that weight loss or sodium restriction, in hypertensives controlled for five years, more than doubles success in withdrawal of drug therapy.

Differential effect of salt loading on sodium and lithium excretion in Dahl salt-resistant and -sensitive rats.

Fractional excretion of lithium, as a marker for proximal sodium reabsorption, was determined in normotensive Dahl S rats (susceptible to NaCl hypertension) and Dahl R rats (resistant to NaCl hypertension) before and following an acute sodium load. Baseline mean arterial pressures, inulin clearances, sodium excretion rates, and fractional lithium clearances were not different between the R and S rats. Following the salt loading and despite similar mean arterial pressures and degree of volume expansion, the glomerular filtration rate, urinary flow rates, and absolute sodium excretion rates were greater in R than S rats. The fractional excretion of lithium was also greater in R than S rats. These data demonstrate that, at equal mean arterial pressures, Dahl S rats have a reduced capacity for sodium excretion, and that this defect is present prior to the development of hypertension. Furthermore, the observation that these animals also have a lower fractional lithium excretion during volume expansion suggests that salt loading reduces proximal tubule reabsorption to a lesser extent in Dahl S than R rats. These data suggest that the subnormal sodium and water excretion observed after sodium loading in S rats may be partially due to an abnormality in proximal tubule sodium handling.

Return of hypertension after withdrawal of prolonged antihypertensive therapy, effect of weight loss, sodium reduction, and baseline factors.

The effect of dietary modification on continued blood pressure control after discontinuation of antihypertensive therapy has been studied. Participants who had been treated for 5 years in the Hypertension Detection and Follow-up Program were enrolled and randomly assigned to continue medication, discontinue medication with no dietary intervention, discontinue medication and reduce weight, discontinue medication and reduce sodium groups. Relapse of hypertension was slow, even without dietary modification. Both weight loss and sodium restriction slowed relapse. The severity of the hypertension and the number of drugs required for hypertension control had a marked effect on the rate of relapse. Relapse was slowest in the participants who had attained the lowest blood pressure on therapy.

Detection and follow-up of moderate and severe hypertensive subjects in the Australia community.

A national screening project has detected 989 subjects aged 30 to 69 years with untreated moderate or severe hypertension. The 1-2% incidence of this condition indicates a total of about 100,000 people in the Australian community potentially requiring therapy. The sample showed that half the subjects were previously unaware of a blood pressure problem. Those so detected showed a very high rate (90-7%) of acceptance of advice to see their own doctor. The local doctors confirmed the elevated pressure level in nearly two-thirds of the patients referred, and initiated treatment in a similar proportion.

Report on progress in the Australian National Blood Pressure Study (NBPS).

1. The National Blood Pressure Study (NBPS) is a single blind trial designed to test the efficacy of active drug treatment in reducing complications from mild hypertension (mean diastolic pressure = 95-109 mmHg). 2. Between 1973 and 1975, four centres screened about 104 000 subjects aged 30-69 years, yielding an estimated prevalence of hypertension (greater than or equal to 95 mmHg diastolic) of 16% and of moderate-to-severe hypertension (greater than of equal to 110 mmHg diastolic) of 1-3%. 3. Some 4000 subjects selected for untreated uncomplicated mild hypertension were randomized to either active treatment (cholorothiazide +alpha-methyldopa and/or a beta-adrenoreceptor antagonist as required) or to matching placebos. 4. At 1 year mean pressures had fallen significantly below entry pressures in both groups but in the active group the fall was greater by a margin of 14-4+/-1-3 (SEM) mmHg systolic and 7-1+/-0-7 mmHg diastolic. At 1 year 5% of subjects in the placebo group had been placed on active treatment on the ethical grounds that pressure had exceeded the mild hypertension limit. 5. Trial end-points (death, morbidity from stroke, hypertensive heart and renal disease, and ischaemic heart disease) number 106 (nine deaths) thus far, of which ischaemic heart disease accounts for 71% and stroke 19%. 6. The duration of trial may need to be extended beyond the original estimate of 5 years.

The Australian National Blood Pressure Study: a test of the effectiveness of antihypertensive therapy on the incidence of ischaemic heart disease.

Although hypertension is an acknowledged risk factor in ischaemic heart disease (IHD) the question remains whether antihypertensive therapy is necessarily beneficial. A priori, because coronary atherosclerosis is probably irreversible, the time for effective intervention would seem to be well before the development of clinical manifestations. The Australian National Blood Pressure Study, a long term clinical trial of the treatment of mild hypertension, is in principle better suited than previous trials to answer the question because the trial population selected (4000 subjects aged 30-69) contains substantial proportions of younger age groups (26% below 45) and of females (37%) and none had manifest IHD at entry. Sensitivity to the emergence of IHD in the trial population is increased by including as diagnostic indices angina and ischaemic ECG changes, using suitably objective methods, as well as myocardial infarction and sudden death. Thus morbidity and mortality from IHD which currently accounts for 71% of trial end points (cf 19% for stroke) will effectively determine the outcome of the trial. The occurrence of a substantial proportion of subjects withdrawn from randomised treatment will mean that the question will be answered necessarily in two ways: firstly in respect of those subjects remaining on their assigned treatments and secondly in terms of all subjects initially assigned one treatment or other irrespective of the subsequent need to change treatment on ethical grounds or of the degree of compliance.

The problem of non-compliance in long-term antihypertensive therapy.

Of 1,593 subjects admitted to the Australian National Blood Pressure Study 1 to 2 years ago, a substantial number (391 or 24.5%) ceased attending, in 85% of cases voluntarily. Withdrawal rates were very high in the first 4 months, settling to 5% per annum by the second year. Extrapolation to clinical practice is hazardous but contibutory factors elicited by questionnaire suggest certain management strategies: maximisation of efforts to enlist subject co-operation at the onset of treatment; management of treatment by family doctor or health centre with appointments flexible in time and infrequent in number; minimisation of doctors' ambivalence about treatment effectiveness and the withholding of information from the subject. It is inevitable that a proportion of subjects will reject long-term drug treatment. This adds further weight to the need for research on alternatives such as low salt diets.

Blood pressure and length of stay in Australia of Italian immigrants in the Australian National Blood Pressure Study.

Data obtained from 10,975 Australian-born and 1,717 Italian-born subjects aged 30-69 years in one centre of the Australian National Blood Pressure Study revealed that the Italians had lower systolic and diastolic blood pressures compared with Australians of the same age and sex. The Italians' blood pressures rose in successive age groups and at the same rate as in the Australians. After the effect of age was eliminated, the duration of residence of the Italians in Australia had a small but significant association with their blood pressures, possibly indicating exposure to blood pressure-elevating environmental factors in Australia.