............ Pascal ( 1657).

Hypertension remains even now a very large public health problem. Around 50 million Americans and a lot more elsewhere have elevated systemic pressure. Whereas hypertension in general can be treated successfully, the current approaches are less than optimal. A small quotation from a recent editorial in the British Medical Journal will strengthen my point.(1) Managing high blood pressure today is " evidence based or evidence burdened? ask Prof. David Sackett of Oxford, and Dr. Rodney Jackson of Auckland, both of whom had been the authors of two of the five guidelines for the treatment of high blood pressure, viz.: British, Newzealand, Canadian, United States, and the WHO. The recommendations of all these guidelines differ from one another. They are inconsistent and unclear on the absolute benefits of treatment. Overall these guidelines agreed for only 31% of patients.
Be that as it may, let us analyze the scenario objectively, with special reference to the multitude of controlled studies in this field, starting from the VA study of severe hypertension management, published in the JAMA in 1967, the study having started in 1964 (2). This study will not stand the strict scientific scrutiny of the present time, but nobody, in his wisdom, will question the validity of treating severe high blood pressure with drugs, although we now know that severe high blood pressure patients with advanced renal damage get very little benefit from aggressive treatment, compared to those without renal failure, where the mortality changes with adequate treatment. (3) The same can not be said of the millions of people diagnosed to have mild to moderate hypertension. Here the diagnostic and the therapeutic decisions have to be made with great care. "Just as war is too serious a matter to be left to the generals alone, hypertension management is too complicated a matter to be left to doctors alone", was the opinion of Professor Thomas Pickering.
Let us consider the following factors in the management of mild to moderate hypertension. The MRC trial of mild hypertension, the largest of the lot with 85,000 patient years of experience in treating nearly 18,000 patients, showed that one has to treat 850 patients to save one individual from stroke. (4) Recently it was shown that 58 elderly people had to be treated for five years to prevent one cardiovascular death compared with 205 people to be treated in middle age to prevent a single CVS death. (5) Many factors, other than systolic and diastolic pressures, influence the decision and the outcome of treating mild to moderate hypertension. Presence of diabetes, left ventricular hypertrophy, and smoking, increase the risk of cardiac events in these patients and their treatment should be adequate. Only one guideline recommends the absolute risk criterion for treatment, and that is the NewZealand guideline. "When that was taken into consideration, half of the patients with uncontrolled hypertension by the United States criterion would be treated unnecessarily and 31% of those classified as having controlled hypertension by the Canadian guidelines would be denied beneficial treatment" was the opinion of Fahey and Peters. (6)
One of the definitions of hypertension is "the level at which inaction may be more damaging than action" - this boils down to the level at which "the benefits of treatment far outweigh its side effects". The benefits gained differ in the elderly as compared to the young and, in those with other cardiovascular risk factors compared to those without any other risk factors. There have been no prospective studies showing the long term outcome of treating those with mild to moderate hypertension, without any other risk factors. It will be impossible to predict that.
In a dynamic system like the human body, the final outcome of any intervention depends on the total initial knowledge of the organism. All the randomized controlled studies referred to in this context have taken into consideration the measurable parameters of man’s phenotype. They have not been able to assess the genotype and his mind. As such, the future predictions are not likely to be accurate at all. Even a minor deviation in the initial state may result in major changes in the final outcome. In addition, changing the initial state may not have the same beneficial effect, as time evolves and the organism changes. (7) Science is difficult. Nothing is as simple as we think. To quote an oft repeated dictum in medicine - that diet high in saturated fat and cholesterol increases the risk of heart attacks, does not mean that reducing fat reduces the risk of heart attacks. Similarly we have this dictum that high blood pressure increases the risk of heart attacks and strokes; but does it mean that lowering blood pressure with drugs lowers this risk proportionately ? Both these assumptions are not scientifically true. I call this the banana logic. Banana has yellow skin, and therefore, anything having yellow skin should be banana. This logic does not hold good in the dynamic human system. Studies have shown that while only a minority of stroke patients are hypertensive, majority of them have been high salt eaters. One could argue that salt intake is a better predictor of stroke than hypertension. (8) A recent Harvard study of a large cohort of men showed that "a firm conclusion regarding the role of dietary fats to risk of coronary heart disease is unwarranted". (9) The link between fat in the diet and the risk of heart attacks and coronary artery disease is not straightforward as was being taught for years. Similar is the story of blood pressure and its lowering with drugs.
The story of controlled trials itself is open to debate. How far are we justified in relying on these type of studies in the present context of our knowledge of the human organism ? A recent review in the journal "Surgery" had a very important lesson to all of us. (10) Of the total of 202 randomized studies reviewed there showed a qualitative score of only 0.40 on a scale of 0-1, which works out roughly 40% of the time the conclusions may be right and 60% of the time they are wrong. Many other studies in this direction have given varying results at the end of the day. Our reliance on this kind of studies has its drawbacks.
In addition to all these is the patient with raised blood pressure. Lowering that with drugs makes life miserable for most of them.This provoked the great champion of hypertension, Late Sir George Pickering, to state that lowering blood pressure with drugs will rob man of all the guarantees enshrined in the preamble to the American constitution written in the year 1772 of "life, liberty, and pursuit of happiness". The shopping plaza labeling of hypertension, in the USA, led to a sudden spurt in sick absenteeism, and the efforts were given up.
Let me quote present statistics to show how difficult it is for both doctors and patients to take a decision to embark on life long antihypertensive therapy. "For a 60 years old male smoker with pre-treatment diastolic blood pressure of 90 mm Hg, a ratio of total cholesterol to high density lipoprotein cholesterol of 6.5, and a normal electrocardiogram, the number needed to treat for one year (to prevent on major cardiovascular event) would be 75. In comparison, it would be 320 for a non-smoking 50 year old woman with considerably higher diastolic pressure (100 mm Hg), a ratio of total/HDL cholesterol of 6.5, and a normal electrocardiogram". (11) This shows the influence of other risk factors in the outcome of hypertension treatment. A simple answer like treat all pressures above a particular level looks simplistic.
In the concluding paragraph of their editorial in the BMJ, Sackett and Jackson have this message. "....Have been overburdened by evidence which gives undue emphasis to the relative risks of raised blood pressure and the relative benefits of reducing blood pressure. We think it is time to consider basing guidelines on clinically more useful absolute measures of the effects of treatment. "In an article in the Bulletin of the V.H.S. Madras, years ago, I had expressed the similar sentiments. (12) That article generated lot of anger against me in our circles. Swimming against the current is difficult. But if one has the courage of conviction and tries to audit one’s own patient care data rigorously, one quickly realizes the folly of following guidelines, based on data from controlled studies done on a different population in a different environment. Hypertension is basically an environmental disease in the inter-population set up, whereas it is mainly genetic in the intra-population set up. (13)
My problems in treating hypertension are two fold. While it is very easy to show fall in blood pressure in some individuals, it is very difficult to get the target blood pressure in some others, despite our best efforts. The difference here is not as simple as mild or severe hypertension ! Some patients are resistant to drug therapy vis-à-vis their blood pressure levels. I do not know if they get any benefit from our efforts at all. Resistant hypertension, in my opinion, is not necessarily severe hypertension, but that group of hypertensives, where it is very difficult to get the pressure down to the desired level despite best efforts. (14) All the studies done so far have not given unequivocal results about management of hypertension, they all agree that individualization of the drug choice will have to wait until we have better data from large, randomized, long term morbidity/mortality trials of newer drugs, as we have for diuretics and beta-blockers. Several such trials are under way. One such is the ALLHAT trial. The results should be ready in the next six years or so. We can hope to enter the 21st Century with better data on treating this enigma called hypertension ! (15)
If one audits his practice in this area I am sure one comes up quickly with many problems. While we are very good in reducing the marginally elevated pressures, most of the latter may, in fact, be normotensives, if observed carefully over a period of three to six months, ( in some, this temporary elevation in the pressure may be for the good of the organism) (16), we can not get the target blood pressure control in many others with genuine raised blood pressure. I think this is our real dilemma.

REFERENCES:

1. Sackett DL, Roseberg WMC, Gray JAM et al. Evidence based medicine : what is it and what it is not. BMJ 1996;312:71-72.
2. Freis E D. Effects of treatment on morbidity in hypertension. JAMA 1967;202:116-12.
3. Hegde BM. Hypertension-the other side of the coin. Jr. Assoc. Physi India 1988;36:324-330.
4. MRC Working Party-Principal Results. BMJ 1985;291:97-104.
5. Marrow CD, Cornell JA, Herrara CR. Et al. Hypertension in the elderly-implications and generality of randomized trials. JAMA 1994;272:1932-38.
6. Fahey TP, and Peters TJ. What constitutes controlled hypertension ? BMJ 1966;313:93-96.
7. Hegde BM. Chaos - a new concept in medicine. Jr. Assoc. Physi. India 1996;44:167-168.
8. Antonios TFT,and MacGregor GA. Salt-more adverse effects. Lancet 1996;348:250-251.
9. Ascherio A, Rimm EB, Giovannucci EL et al. Dietary fat and risk of coronary heart disease. BMJ 1996;313:84-90.
10. Minerva: editorial review. Randomised trials in surgery. Surgery 1996;119:483-486.
11. Jackson RT., and Sackett DL. Guidelines on management of hypertension. BMJ 1996;313:64-65.
12. Hegde BM. Should we treat hypertension? VHS Bulletin 1984;11:24-26
13. Hegde BM. Genetics of hypertension. Postgraduate Medicine Proc APICON 1996 Katmandu. Pages 7-12.
14. Hegde BM. Resistant Hypertension. In Hypertension - Assorted Topics, Bharathiya Vidya Bhavan 1995. Pages 31 - 36. Eds: Hegde BM, Shetty MA and Shetty MR.
15. Davis VR, Cutler JA, Gordon DJ et al. ALLHAT research group. Rationale and design for the antihypertensive and lipid lowering treatment to prevent heart attack trial. (ALLHAT). Amer Jr. Hypertens 1996;9:342-362.
16. Hegde BM. Materia Paramedica. Jr. Roy. Coll. Physi. Surg. Glasgow 1992; March:18 - 19.

Professor B. M. Hegde.
MD., FRCP(Lond.)., FRCP(Edinb.)., FRCP(Glasg.).,FACC.
Director Professor of Medicine and Dean,
Kasturba Medical College, Mangalore.,India.
Visiting Professor of Cardiology,
The Middlesex Hospital Medical School,
University of London.
Fellow, Indian College of Cardiology,
Fellow, Indian College of Physicians.

[index]