Practical Therapeutics Drugs 18: 312-324 (1979) 0012-6667/79/1000-0312/$03.25/0 © ADIS Press Australasia Pty Ltd. All rights reserved.

Mild Hypertension: To Treat or Not to Treat? J.M. Walker and D.G. Beevers University Department of Medicine, Dudley Road Hospital, Birmingham

Summary

In the second half of this century, morbidity and mortality from cardiovascular disease has reached epidemic proportions. The major risk factor associated with cardiovascular disease has been found. from various epidemiological studies, to be elevated blood pressure. Therefore. a lot of energy has been expended in prospective therapeutic trials in attempting to detect whether treatment of high blood pressure is beneficial. In severe hypertension. where the risk to the individual is considerable, this benefit has been demonstrated with relative ease. However, it has not yet proven possible to show conclusive benefit of treatment in the mild group of hypertensives, which form the vast majority ofpatients seen in general practice. A different approach has been advocated where account is taken of other coincidental cardiovascular risk factors; their presence or absence should help the clinician decide whether to treat or not to treat in the individual case.

Hypertension is common, and is probably the primary risk factor for both heart attack and stroke. The prefix 'mild' denotes no qualitative difference from other forms of hypertension, but only the degree of inevitability with which these complications ensue. It is difficult to define hypertension as occurring at any particular level of blood pressure, so as a practical guide we suggest adopting the criteria of Evans and Rose (1971) that 'hypertension should be defined in terms of a blood pressure level above which investigation and treatment do more good than harm'. One of the main stumbling blocks in hypertension has been

the difficulty in extrapolating from the general to the specific: that is, from epidemiological data to the individual clinical case. However, there are available many safe and effective treatments for hypertension, so the main question must be 'at what level of blood pressure should they be applied?'

J. Prevalence ofMild Hypertension While severe hypertension is relatively rare, mild hypertension is extremely common. The number of

Mild Hypertension: To Treat or Not to Treat?

potential patients is enormous, so there are major possible gains in preventive medicine, and the pharmaceutical industry has not been slow to recognise the implications of treating mild hypertensives. Blood pressure in the community follows an almost bell-shaped frequency distribution curve. Pickering (I 967) has always emphasised the unimodality of this frequency distribution, where clear-cut dividing lines between normality and abnormality cannot be identified. Severe hypertension, as can be seen from table I, is not a common problem for general practitioners; it represents a large risk to the individual but a small risk to the community. Mild hypertension, on the other hand, presents a small risk to the individual but, by virtue of its frequency, a large risk to the community. Therefore, differences in definition of only 5 or 10mm Hg can mean vast differences in the numbers of subjects that might be offered treatment. If such small differences in measurement are important, the accuracy of blood pressure measuring techniques must be considered, and also, information on the variability of blood pressure in individuals examined. Only then can the treatment of mild hypertension be fairly evaluated.

2. BloodPressure Measurement The description of the sounds heard during release of the sphygmomanometer cuff were described by Korotkoff in 1905, and provided the basis upon which all later indirect pressure measurements have been made. The first sound (Kl), as described by Korotkoff, is universally accepted as representing the intra-arterial systolic pressure; the determination of diastolic pressure however, has been much debated, partly because the origin of Korotkoff sounds are not yet clearly understood. The sound of muffling (K4) is used by nearly 50 % of doctors in Great Britain (Hodes et al., 1975; Taylor et al., 1979), whereas the disappearance of sound (K5) has been used in the major therapeutic trials. The average difference between K4 and K5 is only about 5mm Hg but much larger

313

Table I. Prevalence of hypertension (data from the Renfrew screening survey; Barlow et al., 1977)

Diastolic blood pressure

45 to 64 vrs)

No. expected in average general practice 1

'Normotensive' «90mm Hg)

60.2

321

'Mild hypertensive' (90-109mm Hg)

35.0

186

'Moderate hypertensive (110-129mm Hg)

4.3

23

'Severe hypertensive'

0.5

3

% Prevalence

(or and

r:;;

(~13Omm Hg)

1 The total number of patients aged 45 to 64 in an average general practice in England and Wales is 534.

differences are seen in certain circumstances (Short, 1976). Indirect blood pressure measurements tend to overestimate the diastolic pressure measured intra-arterially, but there is a high degree of correlation between these two methods (Holland and Humerfelt, 1964). For epidemiological studies, the advantage of closer interobserver agreement when employing K5 compared with K4, mitigates the minor problem of the occasional absence of sound disappearance (K5) in a few individuals. The different diastolic criteria are trivial when severe hypertension is considered, but at diastolic pressures between 90 and 110mm Hg. a systematic difference of 5mm Hg may mean the difference between offering treatment or withholding it for a large group of people. Since treatment is based on the results of clinical trials, there is a strong argument in favour of adopting the same diastolic criterion as these have done, namely K5.

2.1 Equipment The technique for taking indirect blood pressure has been described in detail (Kirkendall et al., 1967;

314

Mild Hypertension: To Treat or Not to Treat?

Peart, 1977), but some aspects of the equipment are important. The standard cuff size (12 x 24cm) can seriously overestimate blood pressure in obese subjects. Pickering et al. (I 954) derived a correction for arm circumference, but more recently Neilsen and Janniche (I 974) have shown, using a large cuff (I4 x 45cm), that indirect measurements in obese subjects can be as accurate as readings obtained in lean subjects with a standard cuff. Observer errors in the form of digit preference and subjective bias are particularly important where drug trials and epidemiological practice are concerned. Sphygmomanometers have been developed which only permit decoding of the blood pressure level after completion of the measurement, either by way of concealed mercury columns (Rose et al., 1964) or variable zero settings (Wright and Dore, 1970). These machines should be routinely employed in any study considered for publication. Recently, several more or less automatic pressure recorders have become available; some for use at home. There will doubtless be further developments of automated sphygmomanometers but a recent review of seven machines (Huynor et al., 1978) revealed that conventional manual models still offer considerable advantages and the standard design should continue to provide the mainstay of routine clinical practice.

2.2 Blood Pressure Variability with Age, Sex and Race Unfortunately, from the clinical point of view, blood pressure does not remain fixed throughout life, but undergoes changes which differ for age, sex, race and society. Studies in children are scanty, but a rise in pressure occurs in the first two years; thereafter, pressures level off until puberty when a second spurt is seen. Systolic blood pressure rises from middle age until the sixth and seventh decades, after which a drop is noted, particularly in men (Evans and Rose,

1971). This fall in the older age group is important and may underlie the preferential survival of. men with the lower systolic pressures. Studies in American negroes show that in both men and women, blood pressures are significantly higher than in caucasians throughout adulthood; again a fall in blood pressure in the later decades is noted (Paul, 1977). Some studies in less technologically advanced societies, in Northeast Africa by Shaper (1967) and in New Guinea and the Pacific Islands by Lovell (I 967) have not shown the systolic blood pressure rise with age that is seen in the developed world. These observations, although subject to criticisms of size and selectivity, are important in so far as they emphasise the difficulty in deciding on an arbitrary pressure level which is uniformly abnormal. 2.3 Individual Variability The tendency for such seemingly trivial factors as ambient temperature, time of day, and psychological interactions to affect blood pressure goes some way to explaining the variability within individuals which is commonly observed. With the advent of techniques for measuring direct,. intra-arterial pressure in ambulant patients, it is to be hoped that the information obtained could improve our understanding of blood pressure behaviour. A circadian rhythm in blood pressure has been demonstrated and pressures fall to low levels during rest or sleep (Millar-Craig et al., 1978). In the meantime, we must rely on the fact that the mean of several indirect blood pressure readings provides a good individual characterisation of blood pressure behaviour; however, such characterisation adds very -little to the prognostic implications that follow a single casual estimation (Gordon et al., 1976).

3. High BloodPressure and Disease The link between high blood pressure and disease of the heart, brain, and kidneys was noted 4,500

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Mild Hypertension: To Treat or Not to Treat?

years ago in the Chinese Medical Treatise attributed to the Yellow Emperor, Huang Ti (2698-2598 BC). Little more than 20 years ago, as effective therapies became available, it was found that treatment of severe blood pressure elevations could improve the previously grave prognosis and reversed heart failure and retinal lesions (McMichael and Murphy, 1955; Smirk et al., 1958). At about this time, data was published showing that symptomless individuals with less severe elevations of blood pressure suffered an increased risk from premature cardiovascular disease (Society of Actuaries, 1959). This information was derived from records kept by Insurance Companies but the rather uncontrolled fashion in which it was gathered limited its usefulness, particularly as the individuals seen by Insurers represent a special subgroup within society. Prospective studies within communities avoid these criticisms. In Framingham, Massachusetts, a sample of the general population has been studied since 1949. Unlike the Society of Actuaries data, in Framingham a relatively small number of observers have been involved and a standardised protocol has been followed which included casual clinic blood pressure readings, recording the diastolic pressure at the sound of disappearance (Kannel, 1977). This study has shown that 'hypertension is the most potent and prevalent contributor to cardiovascular morbidity and mortality', from heart attack and stroke in particular (Kannel and Dawber, 1974). In Britain, Miall and Chinn (I 974) studied a mining community and the neighbouring agricultural area for more than 15 years. As in Framingham, a regular step up in the incidence of cardiovascular events and cerebrovascular accidents was observed for each increment in systolic and diastolic pressure. These three major epidemiological studies were unable to discern a particular blood pressure value which could demarcate dangerous from safe levels. However, in a reanalysis of the Framingham data, Anderson (I978) has challenged this view and suggested that there may be a threshhold for diastolic pressure (less than 90mm Hg) below which the association with cardiovascular morbidity and mor-

tality becomes less significant; this only becomesclear when the statistical smoothing of data performed in the Framingham study is removed. This threshold, however, may have been caused by digit preference, since the Framingham observers did not use random zero or the 'Rose box' type of sphygmomanometers.

4. Systolic versus Diastolic Pressure Systolic and diastolic pressures are highly correlated; nevertheless, there has been a tendency to regard diastolic pressure elevations as more dangerous. Results from the epidemiologicalapproach to hypertension have refuted this view and, in the older age group in particular, systolic pressure elevation alone or in conjunction with diastolic hypertension have been demonstrated as powerful discriminants of cardiovascular risk (Gubner, 1962; Kannel et al., 1970. The importance of systolic pressure is further emphasised by the recent report that systolic pressure achieved from treatment is a better predictor of stroke than diastolic pressure (Beevers et al., 1978).

4.1 Hypertension versus Normotension Pickering (1967) has consistently presented the argument that 'the division of arterial pressure into normotension and hypertension is, scientifically speaking, in the nature of an artefact'. He is highly critical (Pickering, 1978) of the World Health Organization's approach, which has adopted the level of 160/95mm Hg as the upper limit of normality. Kaplan (I978) points out that life expectancy is reduced at all ages in both sexes when diastolic pressure is above 90mm Hg. Systolic pressures of > 130mm Hg appear harmful to men and > 160mm Hg to women, irrespective of other risk factors. Having found that hypertension, at any level, is associated with significant mortality and morbidity, the uninitiated might wonder why all such cases are not offered treatment. However, the attitude of the

Mild Hypertension: To Treat or Not to Treat?

practising clinician should be one of prudence, requiring evidence that treating hypertension is firstly effective in decreasing blood pressure and secondly, that it prevents complications.

5. Evidencethat Treatment ofBloodPressure Affects Outcome The second, pragmatic approach to defining a disease is that suggested by Evans and Rose (I 97 I) [see introduction]. The levels of blood pressure at which drug therapy have been shown in clinical trials to reduce morbidity and mortality are considered below. 5.1 The Chelmsford Study The first controlled trial by Hamilton et al. (1964) from Chelmsford, England, studied 61 patients of both sexes with uncomplicated 'benign' essential hypertension for between 2 and 6 years. All had moderate to severe disease, the criteria for inclusion being a maintained outpatient diastolic pressure of greater than 110mm Hg. In men, a clear benefit of treatment was shown with no complications occurring in 10 cases compared with 8 complications observed in the 12 untreated men. In women, the results were less clear cut, at first glance. However, a more detailed examination of the results revealed that 4 of the 5 complications in the treatment group occurred in women whose blood pressure was poorly controlled; i.e. blood pressure was consistently greater than 200/11 Omm Hg. If these women are considered on the basis of blood pressure reduction versus no reduction, then significant benefit was demonstrated.

5.2 The Veterans Administration Studies The Veterans Administration (VA) studies in men provided the first evidence from a randomised prospective placebo controlled trial, that treatment might be of value in a 'milder' group (Veterans Ad-

316

ministration Cooperative Study Group, 1967, 1970, 1972). The most important criticisms of this study revolve around the necessarily selected group of patients and the severity of their disease. Only men of average age 50 to 52 years, were studied; over 20 % were more than 60 years old and these men suffered nearly two-thirds of all the complications in the untreated group. The diagnosis of hypertension was established on the basis of the mean of blood pressures obtained between the fourth and sixth day in hospital. Those whose diastolic pressures remained persistently between 90 and 114mm Hg were considered for the trial. The patients, therefore, can be regarded as having had more severe hypertension than cases with similar levels of blood pressure obtained in outpatients or general practice. This view is supported by the higher than expected incidence of complications in the control group which suffered a 55 % morbidity risk in five years. At the outset, 22 % of the control and 29 % of the treated group had radiologically enlarged hearts; electrocardiographic (ECG) evidence of left ventricular hypertrophy was seen in 16 % of both groups. This can be compared with a frequency of radiological cardiomegaly of 17 % and ECG ventricular hypertrophy of 5 % found in a population of men with blood pressures greater than 175mm Hg systolic and 115mm Hg diastolic in a survey in Sweden (Berglund et al., 1978). In all, 55 % of the control group plus 60 % of the treated group in the VA trial exhibited one or more abnormalities associated with long standing disease. The VA study confirmed that treatment caused a fall in blood pressure, and these patients suffered no cardiac failure, accelerated hypertension, renal failure or dissecting. aneurysm. They also had a marked reduction in the incidence of strokes; this was clearly demonstrated for pressures between 105 and 114mm Hg, but less convincingly for men with pressures between 90 and 104mm Hg. However, no significant difference in the incidence of coronary events was seen between the two groups. The trial administrators reasonably inferred that the numbers of patients and the length of the study precluded any definite conclu-

317

Mild Hypertension: To Treat or Not to Treat?

sions being drawn with regard to the role of treatment in the prevention of premature coronary heart disease (VA Cooperative Study Group, 1967, 1970, 1972).

5.3 The USPHS Study The United States Public Health Services Group (USPHS, 1972) studied a much milder group of hypertensives of both sexes with sustained diastolic blood pressures of 90 to 115mm Hg determined by self measurement at home and outpatient clinics. None of these subjects had target organ damage at randomisation and their average age was 44 years. Thus, the trial promised to answer many of the criticisms levelled at the VA studies. Those treated received a fixed dosage of chlorothiazide with rauwolfia serpentina and an average diastolic pressure fall of IO.4mm Hg was recorded in this group. There were only I7 major cardiovascular and cerebrovascular events, and these were virtually equally divided amongst the treatment (193 patients) and control groups (196 patients). However, when all complications were considered, 89 compared with 160 occurred in the respective groups, and these differences did not achieve statistical significance. Nevertheless, those events classifted as hypertensive in aetiology were more than twice as common in the placebo than in the treatment group. In the USPHS study, the placebo group fared better than would have been expected from pooled actuarial survival data. Perhaps the intensive surveillance which these patients received was of itself beneficial. The blood pressure did not fall in the placebo patients, although it is interesting that the expected trend of rise in blood pressure with age was not seen.

6. Some Positive Observations A study in Sweden has provided tentative evidence furthebeoo~weff~oftrw~moncoron~

heart disease. In a population screening exerciseof the town of Goteborg, it was noted that men with blood pressures :> 175/ :> 115mm Hg suffered a 3.1 % incidence of coronary heart disease if they were undergoing treatment for hypertension compared with 6.9 % for those men who remained untreated over a mean observation period of 4.3 years (Berglund et al., 1978). Stewart (I 976), in a hospital based study, noted that the incidence of first myocardial infarction in moderately severe hypertensives on treatment containing a ~-adrenoceptor blocking drug was 7.5 % compared with an incidence of 31 % in a comparable group of hypertensives being treated with a combination which did not contain a ~-blocker. These studies, although helping to redress the balance from the nihilistic conclusions suggested from the earlier trials, do not fulfil any of the rigorous criteria which would permit the adoption of wholesale treatment programmes. It has always been surprising that while blood pressure elevation is the major determinant in the development of coronary heart disease(Royal Collegeof Physicians, 1976), the reduction of blood pressure cannot easily be shown to have any effect on the frequency of these complications. Some of the problems encountered in achieving scientifically acceptable evidence of benefit include the large numbers and the length of time necessary to provide a definite answer.

7. Current Trials Mild hypertension in asymptomatic patients is actively being investigated in the United Kingdom, Europe and Australia. The Medical Research Council (MRC) in Great Britain has recently published the results of a pilot trw designed to test the feasibilityof setting up a treatment trial for younger adults with diastolic pressures of 90 to I 10mm Hg (MRC Report, 1977). It is estimated that some 18,000 patients will have to be followed for up to five years in order to detect a 40 % effectiveness of treatment with a 95 % degree of confidence.

318

Mild Hypertension: To Treat or Not to Treat?

In Australia, a large scale trial which had been underway for some years (Abernethy et al., 1976) has recently been discontinued. The Management Committee of the Australian National Blood Pressure Study felt it was ethically unjustifiable to continue to withhold active treatment from patients with diastolic pressures of 1OOmm Hg and above (Reader, 1979). This decision was influenced by the demonstration of statistically significant stroke prevention for diastolic blood pressure ;> 100mm Hg : untreated patients had 20 strokes compared with 8 occurring in the treated group. However, no conclusive prevention of coronary heart disease was demonstrated : the number of events was very small, although greater in the placebo than in the treatment group. Further, no significant differences between the groups were observed in subjects with diastolic pressures of up to 100mm Hg. These patients have had all medications withdrawn and are to be followed closely. The failure of this trial to answer the specific and crucial question of whether treatment of mild hypertension is able to prevent coronary heart disease, has encouraged the Medical Research Council in Great Britain to continue with its own trial. In Sweden, a multicentre trial in mild hypertension has been designed specifically to investigate the possibility that ~-blockers, as opposed to thiazide diuretics, have a special role in reducing cardiovascular morbidity in mild hypertension (Wilhemsen, 1975). Another specialised but numerically important problem is being tackled by the European Working Party on high blood pressure in the elderly (Amery et al., 1978a). So far, only 450 patients aged over 60 have been randomised to receive either a diuretic combination or placebo. Minor electrolyte disturbances in the treatment group have already been noted but the balance between the decreased risk due to blood pressure reduction and the possible increased risk accompanying the rise in blood glucose and uric acid has yet to be determined. It is hoped that these trials will be able to demonstrate whether ~-blockers confer extra benefit in preventing heart disease and whether biochemical side effects of thiazide diuretics, which increase known risk factors, are important.

Another possible hazard of detecting and treating symptomless mild hypertensives is that the anxiety induced in patients may outweigh the beneficial effects of blood pressure reduction. Preliminary observations from the MRC trial demonstrated that far from precipitating neuroticism in previously asymptomatic individuals, there was some improvement in psychological well being (Mann, 1977). By contrast, a report from Canada, noted increased absenteeism from work in newly labelled hypertensive men following a screening survey in a steel mill (Haynes et al., 1978). This absenteeism, which averaged a five day increase per year, could not be accounted for by increased illness due to side effects from medication and was most obvious in those who were less compliant than the average with their medication. This is an important observation which is at variance with the MRC's experience and one is tempted to ascribe some importance to the latter trial being based in the subjects' family general practice, a thoroughly familiar milieu already associated with primary health care. Much of the Canadian programme was carried out during working hours, perhaps initiating a subjective association of time off work with the presence of a newly diagnosed condition: 'hypertension'.

8. Multiple Risk Factor Approach When attributing risk to elevations of blood pressure, there are complications due to the influence of other factors contributing to the risk of cardiovascular disease. These factors generally fall into three groups: I. Unchangeable individual characteristics such as family history, race, sex and age 2. Individual habits such as smoking, obesity, an unhealthy diet and physical inactivity 3. Certain aspects of the environment, from such variables as hardness of water to the nebulous concept of stress (Royal College of Physicians, 1976). At present, a trial in the USA has been designed to investigate whether the multiple risk factor approach

319

Mild Hypertension: To Treat or Not to Treat?

is feasible in hypertension (MRFIT Research Group, 1978). After one year, these workers have been able to produce a mean diastolic pressure fall of 10mm Hg with treatment and a mean reduction in weight of 101b in the participants. Changes in blood levels of lipids and uric acid have also been followed. Whether any of these changes will materially affect morbidity and mortality is keenly awaited, but the results are liable to take many more years. The benefits of lipid lowering agents are very marginal, but patients who have high lipids and high blood pressure have an increased cumulative risk, and a multiple risk factor approach seems logical.

9. Screening Since all but the severest hypertensives tend to be symptomless (Al-Badran et al., 1970; Weiss, 1972) about half the population considered to be at risk will remain undetected without special efforts. Screening surveys using staff and equipment imported into communities have provided an immense amount of epidemiological data. They suffer from the drawback of expense and difficulty in communicating with existing primary health care teams. They also are poorly suited to follow up cases, being unable to achieve the high follow up rates which most general practices can manage on a purely casual basis. It is questionable also whether these transient campaigns could provide the long term commitment which would be required. They do, however, provide a very tangible stimulus and increase awareness in the population, perhaps encouraging more vigilance in doctor and patient alike. Screening at the place of work suffers most of the disadvantages of mobile screening teams, and also carries the difficult burden of confidentiality, where employees may wish not to reveal they are hypertensive to their employers. It is difficult to escape the conclusion that general practitioners could provide an excellent screening service for patients, if only by measuring blood pressure in all attenders in the middle age group; in Great Britain, 80 % of people in this age group visit their

Table II. Mild hypertension: Summary of current recommendations

1. Detection a) Blood pressure measurement in all casual attenders to hospital and general practice in the middle age group b) Blood pressure measurement in all members of high cardiovascular disease risk families 2. Treatment a) All patients with diastolic pressure > 110mm Hg or systolic pressure > 160mm Hg b) Patients with diastolic pressure 100 to 110mm Hgif associated with other risk factors or aged less than 50 c) Aim to reduce treated blood pressure to "130/ ,,95mm Hg 3. Investigation - only required if a) Severe (diastolic blood pressure > 130mm Hg; systolic blood pressure ~ 200mm Hg) b) Resistant c) History suggests likely secondary hypertension d) Young

general practitioner once in three years (Beevers et al., 1975). Some 50 % of hypertensives are already detected, but of these, only 20 % receive treatment (Barlow et al., 1977). Clearly increasing the proportion of known hypertensives that are treated would be a reasonable short term goal to be achieved before more energy is devoted to discovering even more cases.

10. How Effectiveis Treatment? Although effective antihypertensive medication is readily available, various factors tend to prevent the ideal of normal blood pressure (however defined) being achieved in all treated cases. This is important, as the degree of control (or achieved blood pressure with treatment) is one of the strongest prognostic indicators for risk of stroke and cardiovascular disease (Beevers et al., 1978). Apart from doctors withholding treatment - an occurrence as common in hospitals (Heller and Rose,

320

Mild Hypertension: To Treat or Not to Treat?

1977) as in general practice - patient compliance is the most significant practical barrier to good blood pressure control. The former must be tackled by better postgraduate education and the latter can be improved when simple drug regimens with few side effects are given. Efforts to reduce the inconvenience of hospital attendance and to create good relationships between doctor and patient should also be beneficial.

risk associated with it, which for any individual may negate the benefit from treating mild hypertension, is a worrying prospect which must await confirmation. At the moment, however, there are not enough data to justify abandoning these simple and effective antihypertensive drugs.

11. Therapy ILl Drugs A critical review of the vast antihypertensive armamentarium which has grown up over the last 20 years is beyond the scope of this article. Two classes of drugs above all have been adopted as first line therapies for uncomplicated mild hypertension; these are the thiazide diuretics and more recently, the ~­ adrenoceptor blocking agents.

11.1.1 Thiazide Diuretics The thiazides are very effective in producing a fall in blood pressure and their antihypertensive action seems not to diminish with time (Beevers et aI., 1971). In practice, their side effects are minimal (Miall et al., 1976) but the metabolic changes which they induce hypokalaemia, hyperuricaemia, glucose intolerance and serum lipid changes - may be of some clinical importance. The latter have been postulated as a possible cause for the lack of effectiveness of hypertensive treatment in prevention of coronary heart disease in the major clinical trials. This provocative suggestion was raised by Ames and Hill (I976) following a study of 74 mild hypertensives. They found that diuretic treatment tended to raise serum lipids and the rise, though small, might have been enough to cancel out the benefits of reduction of blood pressure amongst mild cases. Thiazides also tend to raise blood glucose (Amery et al., I978b), which most likely presents a risk factor for coronary heart disease itself (Epstein, 1973). That one of the standard treatments available, although very effective and safe, may have a small

>

11.1.2 ~-Adrenoceptor Blockers Theoretically, the ~-blockers may provide a more hopeful approach, particularly because of their antilipolytic action. Some tentative evidence for their cardiovascular protective effect has also been provided by a clinical study (Stewart, 1976). However, this theoretical promise has been dampened somewhat by the findings of several metabolic studies showing confusingly different effects on lipids by various ~-block­ ing agents (Newman, 1977). A recent longer term investigation showed that the only consistent metabolic change was an increase in serum triglycerides after six months treatment; this effect was greater with propranolol than with atenolol (Day et al., 1979). The consequences of these changes are unknown. 11.1.3 Dothe Risks of Drug Therapy Justify Intervention in Mild Hypertension? These observations further highlight the problem of embarking on therapy for the huge numbers of mild hypertensives in the population. Most clinicians should be exceedingly cautious, lest intervention in this group of asymptomatic individuals should reveal more unexpected problems. A mildly reassuring finding was reported by Beevers et al. (I978) in an analysis of the effectof treatment on 1247 patients, in whom no excess of heart disease associated with thiazide treatment was detected. In this retrospective analysis; those who were treated with a combination of thiazides and ~-blockers did best of all.

II. 2 Weight Reduction The association of hypertension and excess weight is beyond any doubt, as has been recently emphasised by a study of one million Americans (Stamler et al.,

Mild Hypertension: To Treat or Not to Treat?

1978). Ramsay et al. (1978) clearly demonstrated that in a hypertension clinic, significant weight reduction could be achieved and that this was accompanied by a fall in blood pressure. In the USA, the preliminary results of the MRFIT Research Group trial have only shown a mean diastolic pressure fall of 1.6mm Hg for a mean weight loss of 101b (4.5kg). The other benefit of weight reduction seen by the Scottish team, was a significant improvement in blood pressure control with less frequent increases in antihypertensive medication doses (Ramsay et al., 1978). I I .3 Dietary Salt

The possible role of salt in essential hypertension is highly controversial. The epidemiological association between high salt intake and hypertension was raised by Dahl and Love (I 957). The rice-fruit diet advocated by Kempler, demonstrated that blood pressure could be reduced, by severe dietary salt restriction. Antihypertensive medication, however, has become available which is more potent and easier to adhere to than the rigorous and unpalatable diets that are low in salt. Opinions differ, but as recently as 1975 an editorial in the Lancet concluded: 'current practice allows no place for salt restriction in the management of hypertension' (Editorial, 1975). The benefits of salt restriction may simply be due to the coincidental reduction in weight. Nevertheless, the western diet can contain up to 20 times the physiological salt requirement and less than drastic reductions would be a safe recommendation for mild hypertensives. I 1.4 Smoking Habits

Both epidemiologicaland clinical studies have consistently failed to demonstrate any relationship between cigarette smoking and hypertension (Greene et al., 1977; Kannel et al., 1967; Ballantyne et al.; Fife, 1978), the only exception being the rare condition of malignant phase hypertension (Bloxham et al., 1979). Smoking, is however, a potent risk factor for coron-

321

ary heart disease and, in conjunction with hypertension, risks are cumulative. The known beneficial effects of cessation of smoking on coronary risk (Royal College of Physicians, 1976) must be advantageous to the hypertensive patient who must therefore be encouraged to give up the habit.

12. Conclusions While mild to moderate elevations of blood pressure form an added risk to health and longevity, therapeutic success has only been proven for cases with diastolic pressures of 11Omm Hg or more (Veterans Administration, 1972). However, a great deal of circumstantial evidence exists which supports attempts at blood pressure reduction. Although proof of improvement in risk from cardiovascular disease is lacking, benefits in prevention of progression to more severe hypertension (Veterans Administration, 1972; Smith, 1977) or occurrence of strokes (Beevers et al., 1973a,b), whether for the first time or as a recurrence (Marshall, 1964), seem to be more clearly established. The co-ordinator of the USPHS Cooperative trial concluded from their experience: 'many mild uncomplicated hypertensives can be appropriately managed by general health interventions, weight control, moderate salt restriction, cessation of smoking and reasonable exercise' (Smith, 1977). While the benefit of these interventions has not achieved the kind of scientifically acceptable proof demanded for drug treatment, their safety cannot be challenged. Clearly, the management of the individual cannot be generalised, but the multiple risk factor approach would seem to give a rational plan for action, until the results of ongoing prospective treatment trials are known. It might be said with some justification that all therapeutic interventions are in the form of an experiment and if middle aged people with diastolic pressures less than 100mm Hg are to be given medication, they ought to be taking part in randomised clinical trials. The situation is so complex that meaningful answers will not be obtained in any other way.

322

Mild Hypertension: To Treat or Not to Treat?

There is little doubt that case detection can be achieved best by recording blood pressures of all adults attending general practice surgeries. Cases that require close observation can then be identified and appropriate treatment given to those with more severe disease. With good organisation, fewer subjects would be overlooked and truly preventive medical care could be achieved.

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Mild Hypertension: To Treat or Not to Treat?

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Author's address: Dr J.M. Walker, University Department of Medicine, Dudley Road Hospital, Birmingham, BI8 7QB (England).