Preventing CHD: why treatin g hypertension is not enough

Transcription

1 Preventing CHD: why treatin g hypertension is not enough N R POULTER, MRCP; S McG THOM, MRCP; and P S SEVER, FRCP In the past, the treatment of hypertension particularly mild to moderate hypertension has been something of an act of faith, since evidence that any benefit accrues in terms of CHD has been tenuous. However, the authors advance clear trial evidence to demonstrate that several risk factors notably smoking, hypertension and serum cholesterol exert a synergistic effect on one another. Their management plan takes this into account. Before describing how to manage hypertension, one should first define the reasons for doing so. Although symptomatic relief may occasionally be required, the main reason for trying to control hypertension is that it is a major risk factor for stroke and coronary heart disease (CHD), which together account for over 40% of adult deaths in the UK. The much abused term risk factor here means that hypertension is causally associated with CHD and strokes. Few would argue that hypertension causes stroke but the results o f the hypertension intervention trials have been misinterpreted and have generated the erroneous b elief that elevated blood pressure does not cause CHD. Dr Poulter, Dr Thom and Professor Sever are at The Hypertension Clinic, St Mary s Hospital, London, UK. They wrote this article specially for M o dern M ed ic in e. It is true that most of these trials have failed to demonstrate any significant reduction in CHD events in spite of lowering blood pressure. However, these data should not be considered critical in making judgement as to what causes CHD. Intervention trials have never been an appropriate or efficient tool to investigate the aetiology of chronic diseases because of the difficulty of interpreting a negative result. Such a result may be due to one or more of several reasons (see Figure 1) and it is impossible to determine which reason applies. More important criteria in judging whether an apparent association between a risk factor and disease is causative include the strength of the association and the presence TABLE 1 Baseline systolic blood pressure (SBP) and six-year age-adjusted CHD m ortality in men aged 35 to 57 free of Ml at baseline (MRFIT) SBP (mmhg) n Rata par Relative risk < * , ,7 3, " < > FEBRUARY 1991 / MODERN MEDICINE OF SOUTH AFRICA 55

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3 Preventing C H D continued. I Smokers with a diastolic blood pressure >90 mmhg and a cholesterol level >6,34 mmol /1have a 13-fold increased chance o f coronary death. of a dose-response effect. Such criteria are very well satisfied by the data on the relationship between high blood pressure and CHD. Several prospective studies have shown that increasing levels of blood pressure predispose to in creasing risk of CHD death, the best example coming from the MRFIT study. In this Am erican study, randomly selected men aged 35 to 57 years were screened for CHD risk factors. Table 1 shows the graded effect of systolic blood pressure (SBP) levels on the six-year CHD mortality rate in those without a past m edical history of myocardial infarction. The data for diastolic blood pressure show a similar effect. Extending these data to include two other major risk factors for CHD smoking and serum total cholesterol Table 2 shows the six-year CHD death rates by categories of smoking, BP and cholesterol. From this Table the combined effect of these three common risk factors is clear those smokers with high blood pressure (diastolic >90 mmhg) and high cholesterol (>6,34 mmol/1) have more than a 13 fold increased chance of CHD death than nonsmokers with low cholesterol and low blood pressure (21,4/1000:1,6/1000). A further lesson from MRFIT data can be derived from those who were not diabetic, did not smoke and were in the lowest quintiles of systolic and diastolic blood pressure and serum cholesterol. This group of almost Figure 1. Possible outcomes of a trial designed to monitor the effect on a disease (eg CHD) of lowering a major risk factor for that disease (eg blood pressure) men had a CHD mortality rate less than that of Japanese men who have the lowest CHD mortality rates of any industrialized country in the world. In the light of these data it is very difficult to avoid the conclusion that blood pressure, serum cholesterol and smoking are causally related to CHD and, furthermore, that these three factors are the main determinants of the current CHD epidemic prevalent in Figure 2 The folly of trying to base hypertension management on blood pressure alone. FEBRUARY 1991 / MODERN MEDICINE OF SOUTH AFRICA 57

4 Preventing CHD continued I It is difficult to avoid the conclusion that blood pressure, serum cholesterol and smoking are causally related to CHD. the UK. Returning to the disappointing results of the trials which in general failed to dem onstrate a significant reduction in CHD in spite of lowering blood pressure levels, two important lessons are evident to guide the management of hypertension. The first concerns the interaction and high prevalence of smoking and elevated serum cholesterol in hypertensives. Increased risk of CHD due to serum cholesterol begins at approximately 5 mmol/1 and rather more than two-thirds of hypertensives are above these levels. Since the presence of more than one risk factor in an individual probably produces more than an additive effect of the risk from each independent factor, and elevated serum cholesterol seems to be the pivotal risk factor for CHD, it is clearly vital to address smoking, serum cholesterol and the other risk factors along with blood pressure. Figure 2 illustrates the folly of trying to base hypertension management on blood pressure levels alone. A second lesson suggested by the trials relates to the effect of hypotensive agents on lipid profiles. There is a continuous, graded, causally-related effect of total serum cholesterol upon risk of CHD, and a protective effect with increasing levels of HDL cholesterol. The drugs most commonly used in the trials (beta-blockers and diuretics) have been shown to have adverse effects on lipid 58 MODERN MEDICINE OF SOUTH AFRICA / FEBRUARY 1991 TABLE 2 Six-year age-adjusted CHD death rates (MRFIT) Serum cholesterol qulntile DBP <90 mmhg DBP >90 mmhg (mmo!/l) rate/1000 rate<1000 Nonsmokers 1. (<4,71) 1,6 3,7 2. (4 71-5,22) 2,5 4,0 3. (5,35-5,69) 2,7 5,6 4. (5,72-6,31) 3,8 5,6 5. (>6,34) 6,4 10,7 Smokers 1. (^4,71) 5,2 6,3 2. (4,71-5,22) 5,5 10,0 3. (5,25-5,69) 7,3 15,5 4. (5,72-6,31) 10,2 16,6 5. ( 6,34) 13,3 21,4 profiles. It is, therefore, not surprising that the trials failed to demonstrate the expected reduction, based on lowering blood pressure, in CHD-related events. While we do not yet know the long-term efficacy and sideeffects of those new agents which have a neutral or, even better, a beneficial effect on lipid profiles, our best estimate at present must be that they are likely to be preferable to betablockers and diuretics in the prevention o f CHD events. This background has resulted in the evolution at our Hypertension Clinic of the management policy guidelines outlined in the FACTFILE which we believe apply to most hypertensive patients. The decision when to consider blood pressure as abnormal enough to treat with drugs is a difficult one and should be made on an individual basis. However, only benefit or at least no harm can be anticipated from the non pharmacological advice described in the FACTFILE, and the one threshold for making these recommenddations should be very low, particularly since diastolic blood pressure levels above 85 mmhg and/or systolic levels above 140 mmhg are associated with a significantly in creased risk o f ca rd iovascular disease. The treatment decision is influenced by patient age, and the presence of concomitant risk factors invites a more active approach in borderline cases. Current evidence suggests that with standard treatment (betablockers and diuretics), benefit is only to be expected at diastolic levels of 100 mmhg or above. Sadly, no such trial data are yet available for the level of systolic blood pressure,

5 The decision when to consider blood pressure as abnormal enough to treat with drugs should be made on an individual basis. M anagem ent guidelines for hypertension 1. Confirm that the blood pressure really is elevated readings should be taken after a reasonable rest period (10 minutes) and, depending upon the level, two or more sets of readings should be recorded over a period of days or weeks be'ore a decision to treat with drugs can be considered 2. Assess the risk factors for hypertension: Increased body mass Excess ajcohot intake Salt intake: is sail added >o food? are salty fooas ingested? is salt added to cooking? Family history 3. Assess other CHD risk factors: Lipid profile: is serum total cholesterol >5,2 mmol/l? is HDL cholesterol <0,9 mmol/l? (NB a high HDL raises the threshold for action on total cholesterol) Smoking Diabetes Exercise output Oral contraceptive use а. Explain why blood pressure and other risk factors need treatment" 5 Advise on nonpharmacological approach to lowering blood pressure by: Reducing body mass if overmass (decrease kilojoules, increase exercise) Reducing alcohol intake if excessive (ie >two units/day) Reducing salt intake (not adding salt to food, avoiding salty 'ood, reducing salt added to cooking) Increasing intake of potassium-rich goods, eg figs, bananas, etc Involving the spouse and/or other close family in the above measures б. Advise on nonpharmacological approach to other CHD nsk factors: Serum total cholesterol (reduce saturated fat intake, reduce cholesterol intake) HDL cnolesterol (stop smoking, increase exercise) Smoking (stop) Olabetes (lose mass, other standard dietary advice) Exercise oulput, eg walking, swimming, etc (increase gradually). Canadian Airforce exercises are easy to do for patients of all ages Oral contraception (avoid if possible) Involve the spouse and/or close family in the above measures 7. If blood pressuro remains elevated, initiate drug therapy and continue nonpharmacological approach to blood pressure and other risk (actors. Avoid, where possible, drugs with adverse effects on lipid profiles, especially if serum total cholesterol is >5,2 mmol/l and/or HDL cholesterol <0,9 mmol/l 8. Reassess blood pressure and other risk factor status frequently at tirst, and feed back information to the patients as to where progress has and has not been made. Adjust treatment as necessary 9. In young (<40 years of age), severe or refractory hypertensives investigation for "secondary hypertension is recommended 10. If after several months of combined drug and nondrug treatment, blood pressure levels fall to low levels (eg diastolic <75 and/or systolic <120) a gradual reduction of drug treatment should be attempted although it is a stronger predictor of cardiovascular disease. A final message which the hypertension trials have provided is that, in spite of treatment, CHD and stroke mortality and morbidity rates are worse among those in whom target organ damage due to hypertension is established, compared with those without target organ damage. The obvious conclusion must therefore be that the ideal managem ent o f essen tial hypertension and CHD is prevention but, failing that, early intervention seems appropriate. Indeed, for optimal impact on the current cardiovascular disease epidemic, we should perhaps supply the n on pharmacological advice described above to the whole population not just to those with hypertension or angina. FEBRUARY 1991 / MODERN MEDICINE OF SOUTH AFRICA 59