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March 2001, Volume 51, Issue 3


Management of Hypertension: Do We Know all the Questions?

I. A. Khan  ( Department of Internal Medicine. Ziauddin Medical University Hospital. Karachi. )

Hypertension in Pakistan remains a major health problem; with a prevalence of 17.9% in the adult population, there are an estimated 10 million hypertensives1. The effects of hypertension on cardiovascular and renal mortality and morbidity are well-established worldwide2. Unfortunately we know very little about the characteristics of hypertension in our population. There are no studies of enough power dealing with the risk factors, course, management and its effects on cardiovascular mortality and morbidity in Pakistan. There are suggestions from studies on the immigrant population in the UK that the incidence of and rate of complications from hypertension are, in fact, much higher in the Indo-Pakistani community than the Whites3. It is therefore not possible to draw any conclusions about management of hypertension in Pakistan from our local experience. The best we can do is to try to implement the management principles known from international studies, on our population.
The optimal management of hypertension can be approached by asking several questions and trying to answer them with the available evidence. That the treatment of hypertension significantly reduces mortality and morbidity is now established beyond doubt2. Should we treat all hypertensives ? Patients with moderate to severe hypertension, those with other risk factors for cardiovascular/renal complications and those with target organ damage should always be treated. Decision to treat patients with mild hypertension should be individualized based on their risk profile4. Are non-pharmacological measures of an\\ value? This question has not been addressed as rigorously as that of pharmacological intervention. The measures, which have been found to be beneficial are reduction of weight in overweight individuals and aerobic exercise in sedentary people5, increased consumption of potassium6 and magnesium7. A diet rich in fruits and vegetables and low in animal fat also has positive effects8. Reduction of dietary sodium helps lower blood pressure in the majority of hypertensives9. The benefit of these measures is modest; these should be used as primary therapy in people not requiring pharmacological treatment and should be part of the treatment plan for those who do. Are all antihypertensives equally effective in controlling hypertension? Although the response to these medicines varies to some extent with age, sex, stage of hypertension and ethnicity,10 in most clinical situations all classes of drugs have been found to be equally efficacious10,11. (Most
of these have also been studied in small groups of Pakistani patients and found to be effective) The more important question is: are they equally effective in reducing mortality and morbidity? Until recently the only drugs known to have this benefit were diuretics and beta-blockers. Several large studies completed recently have shown that other classes of drugs viz, calcium channel blockers and ACE inhibitors also have similar benefits for morbidity and mortility12-15. Is any class of drugs better than others? This question is more difficult to answer based on the present state of evidence. The factors to consider are: any extra advantages (in general and in specific groups of patients). disadvantages and side effects profile (so-called quality of life issues) of the different classes of drugs over and above their blood pressure lowering effect. The evidence is mixed, at best. Based on some studies claims have been made about the added advantages of ACE inhibitors (and AT-2 receptor antagonists): regression of left ventricular hypertrophy (an independent risk factor for increased mortality)16 prevention and delaying of progression of diabetic nephropathy17 and better tolerance. None of these can be used as an argument for their superiority, however.Most of the regression in LVH can be achived by almost all anti-hypertensive drugs with adequate long term control of blood pressure: in any case reducing LVH independently has never been shown to reduce mortality18. In at least one study there was an increased risk of stroke in hypertensive patients treated with captopril14. In the UKPDS 39 trial there was no difference in onset or progression of diabetic nephropathy in the type II diabetic hypertensive patients treated with either beta-blockers or ACE inhibitors15. Calcium channel blockers have lately received a lot of adverse publicity claiming increase in mortality,19 GI hemorrhage20 and malignancies;21 all of these have been cohort studies with methodological limitations. The ABCD trial showed higher incidence of myocardial infarction in the nisoldipine arm compared with the ACE-inhibitor22. None of the recent, large scale, prospective studies using longer-acting dihydropyridines have shown these adverse effects23,24. Although some studies (in which quality of life was not the primary question) showed better tolerance for ACE individual hypertensive? Pending further, conclusive studies the best approach is to individualize the treatment based on the current evidence; in this regard the patient’s co­morbidities should be the deciding factor4. Patients with contra-indications to any particular class should not receive those drugs. Patients with cardiac disease may derive extra benefits with the use of ACE inhibitors27 and beta-blockers. When choosing calcium channel blockers, longer-acting dihydropyridines should be preferred, especially in the elderly; their use should be avoided in the setting of acute coronary syndromes (except, perhaps, non Q-wave Ml) and decreased systolic function.
Should isolated systolic hypertension (ISH) be treated? There is no longer any doubt that ISH is a strong predictor of cardiovascular events and its treatment reduces the risk28,29.
How should hypertension be treated? The targets of treatment of hypertension in the elderly are the same as in the younger population29. Some drugs (especially diuretics) may be more effective in this setting than others; ACE inhibitors (at least in some ethnic groups) may be less efficacious10 Short acting dihydropyridine calcium channel blockers should be avoided because of concerns for increased mortality. Closer watch and more gradual reduction is advisable to prevent increased risk of falls from iatrogenic orthostatic hypotension and cerebral and coronary ischemia.
Finally how much should the blood pressure be lowered? That blood pressure should always be brought down to the normotensive range is not disputed2,30. The questions are: is there an optimal level which we should try to achieve in every patient and if there is a level beyond which blood pressure lowering may actually be harmful? The latter issue has been popularized by the concept of the i-point. That excessive lowering can cause problems is obvious; what defines ‘excessive’ is not31. Lowering of diastolic blood pressure to a level below 90mm of Hg should perhaps be the goal in most hypertensives.
Any further reduction may offer extra benefits but they are so marginal that the additional costs and side effects are perhaps not worthwhile. Diabetic patients, however, may derive optimal benefits at a diastolic blood pressure closer to 80mm of Hg. Any further lowering in either group neither increases mortality nor confers any additional benefits12. The jury is still out on this question.
Perhaps the most important question in our context is no longer how to treat hypertension; we know the answers to most questions in this regard. The big question is: how to deliver the benefits of treatment to the large number of Pakistani hypertensives. The National Health Survey of Pakistan has some very disturbing statistics1. Sixty-three to eighty-five percent of the hypertensive people are unaware of their disease, less than one third of the aware people are being treated and only six percent of them have their blood pressure under control. These dismal figures are in the backdrop of an average health-care contact rate higher than that in the USA. Perhaps the most significant step towards decreasing the enormous morbidity and mortality due to hypertension is making sure that every person who comes in contact with a health-care provider hes his/her blood pressure checked!


1.National Health Survey of Pakistan 1990-94. Pakistan Medical Research Council, Islarnabad, Pakistan. 1998.
2.Panty BM, Smith NL, Siscovick DS, ct al. H ealth outcomes associated with antihypertensive therapies used as first-line agents: A systemic review and ineta-analysis. JAMA., 1997:277:739.
3.Raleigh VS. Diabetes and hypertension in Britain’s ethnic minority: implications for the future of renal services. Br.Med.J,, 1 997;3 14:209.
4.The sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Arch.Intern.Med., 1997:157:2413.
5.Blumenthal JA. Sherwood A, Gullette EC, et al. Exercise and weight loss reduce blood pressure in men and women with mild hypertension. Arch. lnt.Med., 2000:160: 1947-48.
6.Whelton PK, He J, Cutler JA, et al. Effect of oral potassium on blood pressure. JAMA., l997:277:l624.
7.Shafique M, Din M, Ashraf M. Role of magnesium in the management of hypertension. J.Pak.Med.Assoc., 1993:43:43.
8.Appel Li, Moore JM, Obarzanca E. et al. A clinical trial of the effects of dietary patterns on blood pressure. N.Engl.J.Med.,1997:336:1117.
9.Midgley JP, Matthew AG, Greenwood CMI. et al. Effect of reduced dietary sodium on blood pressure a meta-analysis of randomized controlled trials. JAMA.,1 996:275:1590-92.
10.Matterson BJ, Reda Cushman WC, et al. Single drug therapy for hypertension in men - a comparison of six antihypertensive agents with placebo. N.EngI.J.Med.,1993:328:914-15.
11.Philipp T, Anlauf M, Distler A, et al. Randomized, double blind multicenter comparison of hctz, atenolol, nitrendipine and enalapril in anti hypertensive treatment: results of the HANE study. Br.Med.J., 1997:315:154-56.
12.Hansson L, Zanchetti A, Carruthers SO, ci al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the hypertension optimal treatment (HOT) randomized trial. Lancet, 1998;351:1755.
13.Hansson L. Lindholm LH, Ekbom T, et al. Randomized trial of old and new anti-hypertensive drugs in elderly patients: cardiovascular mortality and morbidity. The Swedish Trial in Old Patients with hypertension-2 study. Lancet, 1999;354:1751.
14.Hansson L, Lindholm LII, Niskanen L, et al. Effect of angiotensin converting enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension - the Captropril Prevention Project (CAPPP) randomized trial. Lancet:1999:353:61 1-15.
15.UK Prospecive Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. Br.Med.J., 1998:317:713-15.
16.Abbas S. Regression of left ventricular hypertrophy with various antihypertensive agents. Pak. Anned Forces Mcd. J., 1997:47:15.
17.Kasiske BL, Kalil RS, Ma JZ, et al. Effect of antihypertensive therapy on the kidney in patients with diabetes: a meta-regression analysis. Ann. Intern Med., 1993:118:129-31.
18.Dunn FO, Pfcffer MA. Left ventricular hypertrophy in hypertension (editorial). N.Engl.J.Med., 1999:340:1279.
19.Furberg CD, Panty BM, Meyer JV. Nifedipine: dose related increase in mortality in patients with coronary heart disease. Circulation, 1995:92:1326­ 28.
20.Pahor M, Guralnik JM, Furgerg CD. et al. Risk of gastrointestinal hemorrhage with calcium antagonists in hypertensive persons over age sixty-seven years old. Lancet, 1996;347:1061-64.
21.Pahor M, Guralnik JM. Ferruci L, et al. Calcium-channel blockade and incidence of cancer in aged population. Lancet, 1996:348:493-94.
22.Estacio RO, Getters PW, Hiatt WR. et al. The effect of nisoldipine as compared with .enalapril on cardiovascular outcomes in patients with noninsulin-dependent diabetes and hypertension. N.Engl.J. Med., 1 998,338:645-47.
23.McMurray J, Murdoch D. Calcium-antagonist controversy: the long and short of it? Lancet, 1997;349:585.
24.Tuomilehto J, Rastenvte D, Birkenhager WH. Effect of calcium-channel blockade in older patients with diabetes and systolic hypertension. N.Engl.J.Med., 1999\'340:677-79.
25.Grossman E, Meserli FH, Golbourt H. High blood pressure and diabetes: Are all antihypertensive drugs created equal? Arch.lnt.Med., 2000; 160:2447-49.
26.Siscovick DS, Raghunathan TE, Psaty BM, et al Diurelic therapy for hypertension and the risk of primary cardiac arrest. N.Engl.J.Med., 1994;330:1852-56.
27.The Heart Outcomes Prevention Evaluation Study lngestigators. Effects of angiotensin converting enzyme inhibitor, ramipril, on cardiovascular events in high risk patients. N.Engl.J.Med., 2000:342:145.
28.Sagie A, Larson MG, Levy D. The natural history of borderline isolated systolic hypertension. N.Engl J .Med., 1993:329:1912-14.
29.Stressan JA, Fagard R, Thijs L. et al. Randomized double blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet,1 997:350:757-58.
30.UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type2 diabetes: UKPDS 38. Br.Med.J.. 1998:317:703-5.
31.Glynn RJ, Field TS, Rosner B, et al. Evidence for a positive linear relation between blood pressure and mortality in elderly people. Lancet, 1995:345:825-26.

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