Pharmaceutical Journal Vol 263 No 7062 p383-386
September 11, 1999 Continuing Education

Hypertension

(3) Management of the hypertensive patient

By Charles Spencer, MBBS, MRCP, and Gregory Lip, MD, FRCPE

The management of the hypertensive patient requires confirmation of the diagnosis, assessment of the patient for underlying cause(s) and target organ damage, and initiation of appropriate therapy.

Confirmation of the diagnosis

The most important aspect of the management of a patient presenting with high blood pressure is to confirm the diagnosis of hypertension. It is a fundamental error to condemn a patient to decades of medication on only one or two casual blood pressure measurements. Except for hypertensive emergencies, or patients in high risk groups, including those exhibiting hypertensive target organ damage, it is good practice to take multiple blood pressure readings over a few months, while pursuing non-pharmacological measures, before instituting drug therapy.
Multiple measurements of blood pressure over a period of time may demonstrate that blood pressure levels fall over time so that a significant number of patients can no longer be regarded as hypertensive.¹ Some patients develop high blood pressure in relation to hospital or clinical attendance, the so-called “white coat” effect. Patients with white coat hypertension do not need antihypertensive therapy but need careful monitoring, as they may exhibit minor vascular changes and, eventually, develop overt hypertension in the future. Use of ambulatory blood pressure monitoring devices has assisted the diagnosis of this condition.²

Initial assessment

Each new patient requires a thorough clinical assessment, which should include a full physical examination. The basic investigations should include blood biochemistry for urea and electrolytes, serum creatinine, fasting glucose and cholesterol, urinalysis for blood, protein and glucose and an electrocardiogram (ECG). In some individuals, further investigations such as an echocardiogram or renal ultrasound may be required.
The first aim of assessment is to exclude secondary causes which, although accounting for less than 5 per cent of hypertensives, are important to identify, as they often are either correctable or represent serious underlying disease. The majority of secondary causes are either renal, endocrine or due to concomitant medication, such as oestrogen-containing contraceptive pills or non-steroidal anti-inflammatory drugs (PJ, August 21, p280).

The second aspect is to establish the individual’s level of absolute risk. A patient with a blood pressure of 145/90mmHg who is a male aged 65 years, a smoker and has already suffered a myocardial infarction will be at much higher risk than a 45-year-old woman with a blood pressure of 160/110mmHg and no other risk factors. Important factors to establish in assessing risk are listed in Panel 1. Evidence of hypertensive target organ damage, such as left ventricular hypertrophy (LVH), proteinuria or severe retinopathy is of particular concern. A number of algorithms are now available to calculate precise levels of cardiovascular risk in individuals, some based on sophisticated computer software.3 Both the World Health Organisation and the American joint national committee on prevention, detection, evaluation, and treatment of high blood pressure use an approach that divides patients into three or four risk categories.4,5 The most powerful predictor of risk in the hypertensive patient is pre-existing cardiovascular disease.

Panel1: Factors for assessing risk in hypertensive patients Risk factor   Age Diabetes Family history Gender Obesity Serum cholesterol Smoking   Target organ damage   Carotid atherosclerosis Diabetic neuropathy Hypertensive retinopathy Left ventricular hypertrophy Proteinuria Renal failure Symptomatic arterial disease   Overt cardiovascular disease   Angina Coronary artery bypass graft Heart failure Myocardial infarction Percutaneous transluminal coronary angioplasty Stroke Transient ischaemic attack

Non-pharmacological management

Before a patient is commenced on antihypertensive medication, it is appropriate to attempt non-pharmacological measures to lower blood pressure, except in a few high risk cases, in whom they should be applied in parallel. A number of lifestyle modifications, such as weight reduction, salt and alcohol restriction and regular exercise may produce significant falls in blood pressure and can also improve other cardiovascular risk factors.
Weight loss in the large number of hypertensives who are obese may reduce blood pressure by about 1.6/1.3mmHg per kg loss and, in addition, may also improve the lipid profile and insulin resistance.⁶ Alcohol excess is an important factor for hypertension and patients should be advised to moderate their consumption to no more than 21 units a week in men and 14 in women.⁷
Dietary sodium intake in most people eating a western diet is grossly in excess of that required for health.⁸ Patients should, therefore, be advised to avoid adding salt to cooking or at the table. Processed foods often contain vast quantities of salt and should be avoided as much as possible.
Some patients use salt substitutes containing potassium chloride; while these may be beneficial, there is a risk of life-threatening hyperkalaemia when these salt substitutes are combined with ACE inhibitors or potassium-sparing diuretics. As it is often difficult to achieve satisfactory blood pressure reductions in black patients and the elderly, who are particularly sensitive to salt, salt restriction may be useful in combination with antihypertensive therapy in these groups.⁹
Many patients avoid physical exertion because they are often afraid that it will do them harm while they are suffering from high blood pressure. However, the converse actually holds true. Taking 30-45 minutes of modest aerobic exercise, such as a brisk walk or a swim, three times a week produces a modest fall in blood pressure.¹⁰ Finally, the most effective lifestyle measure to reduce overall cardiovascular risk is smoking cessation and every effort should be made to encourage hypertensive smokers to quit. Nicotine replacement should be made available where appropriate.

Choice of drug

In the past decade, the philosophy of drug choice in hypertension has moved away from the rigid dogma of stepped care, in which all patients started on a diuretic and then had a b-blocker added if control was inadequate. The modern approach is to take into account the patient’s individual characteristics in terms of concomitant disease and risk factors, as well as social and economic considerations, when deciding on the most appropriate therapy.
The straightforward patient Although a substantial number of people with hypertension have the complications discussed below, many will not. For these individuals, low-dose diuretics and b-blockers are the first choice on the grounds that they have the greatest weight of trial evidence behind them.
Many patients with hypertension fall into a number of special groups, where there are either compelling indications for a particular agent from randomised controlled trial results or good reasons to believe a particular agent will have favourable effects on a co-morbid condition. These are discussed below.
Diabetes mellitus Patients with diabetes suffer from both macrovascular complications, such as myocardial infarction and peripheral vascular disease, and microvascular disease, such as diabetic nephropathy and retinopathy. In type I diabetes, there is clear evidence that ACE inhibitors reduce the progression of both retinopathy and nephropathy and possibly even neuropathy; these drugs should thus be regarded as first-line agents in patients with these complications.^11,12,13
In type II diabetes, the situation is less clear. Trials have demonstrated reductions in proteinuria with the ACE inhibitors, calcium channel blockers and, more recently, b-blockers. Low-dose diuretics have also been found to be as effective in diabetic patients as in non-diabetic patients. Thus, to summarise a rather confusing situation, the ACE inhibitors are probably the drugs of first choice for patients with type II diabetes and proteinuria.
Calcium channel blockers, b-blockers and low-dose diuretics are also suitable in uncomplicated type II diabetes.
Coronary artery disease Patients with overt coronary artery disease are at particularly high risk of further cardiac events.
There is no doubt that b-blockers improve prognosis after myocardial infarction, and thus they are the drugs of choice in hypertensives who have suffered a myocardial infarct. If b-blockers are contraindicated, there are some data to suggest that verapamil may be beneficial if there is no evidence of heart failure. Those with heart failure post-myocardial infarction should receive an ACE inhibitor.
Patients with angina but no previous myocardial infarction should probably also be treated with a b-blocker or calcium channel blocker.
Cardiac failure There are few data on the best drug for those patients with both hypertension and heart failure. However, a number of large trials have been carried out in unselected patients with heart failure, many of whom will have had hypertension. These have consistently demonstrated a survival advantage for those treated with ACE inhibitors and these should, therefore, be the drugs of choice in such patients.¹⁴
Most patients with heart failure will also require a diuretic. Recent studies have found that the addition of a b-blocker, such as carvedilol, bisoprolol or metoprolol, to ACE inhibitors and diuretics in stable patients with heart failure significantly improves mortality.¹⁵
Older patients Many older hypertensives have isolated systolic hypertension. In this group, there is now good trial evidence for the use of low-dose diuretics or long-acting dihydropyridine calcium channel blockers as first-line drugs.^{16, 17}
There are very little data on treating hypertensive patients aged above 80 years. It seems reasonable to extrapolate data on the less elderly to octogenarians who are otherwise in good health. Nevertheless, the approach to the very frail elderly is much less certain and a degree of common sense and wisdom is required.
One ongoing trial, the Hypertension in the Very Elderly Trial (HYVET) will provide data on treating hypertension in patients aged >80 years.¹⁸
Renal failure Many patients with renal failure have hypertension but whether the hypertension is the cause of, or secondary to, the renal failure often remains unclear. There is evidence to suggest that non-malignant essential hypertension does not cause renal impairment.¹⁹ The effective treatment of hypertension slows the progression of renal failure and it appears that ACE inhibitors are most effective in this situation, being renoprotective and delaying the progression of both diabetic and non-diabetic nephropathy.^12,20 The ACE inhibitors should, therefore, be the drugs of choice in hypertensive nephropathy, except in those patients with bilateral renal artery stenosis or stenosis in the artery to a single kidney. The optimal blood pressure should be lower (<125/75mmHg) for those with proteinuria of more than 1g/24hours.²¹
Peripheral vascular disease Peripheral vascular disease is a common problem in hypertensives, especially those who smoke. Vasodilators, such as calcium channel blockers and a-blockers, are useful agents in such patients. There is a misconception that b-blockers may worsen peripheral vascular disease but trials comparing them with placebo did not significantly influence claudication distance.²² Nevertheless, b-blockers should be avoided in patients with rest pain or gangrene. Caution is advised when using ACE inhibitors in those patients with peripheral vascular disease, as renal artery stenosis may be present.
Black patients Black or Afro-Caribbean patients tend to have lower levels of renin than whites and therefore respond less well to drugs that act on the renin-angiotensin system, such as the b-blockers, ACE inhibitors and angiotensin II antagonists.²³ They respond well to calcium channel blockers, a-blockers and diuretics. However, they should not be denied ACE inhibitors and b-blockers when there are clear indications for these agents, such as post-myocardial infarction or heart failure. The combination of a diuretic and another agent is often a good strategy in case of a poor response to a single drug. Indeed, the relative resistance of black hypertensive patients to the b-blockers and ACE inhibitors is abolished by using very high doses or by the addition of a diuretic. Salt restriction is also frequently necessary to achieve good blood pressure control.
Dyslipidaemia Although antihypertensive drugs differ in their effects on blood lipids, they have not proved to make a difference to outcomes. As the b-blockers and high-dose diuretics aggravate hyperlipidaemia, it would seem prudent to avoid their use in patients whose hyperlipidaemia is difficult to control, although in clinical practice the effect of these drugs on cholesterol is small.
In patients at high risk of cardiovascular disease, the HMG coenzyme A inhibitors (statins) have been shown to reduce cardiovascular events.²⁴ The best strategy in patients at high cardiovascular risk who have both hyperlipidaemia and hypertension is to treat both and not worry too much about the small changes in cholesterol caused by the different antihypertensive drugs.

Pregnancy Hypertension in pregnancy is a complex issue that is beyond the scope of this article. The drug with which there is the most experience in the treatment of hypertension in pregnancy is methyldopa. Other drugs with which there is experience include prazosin, hydralazine and nifedipine. However, ACE inhibitors and angiotensin II antagonists are contraindicated in pregnancy as they have multiple adverse effects on the foetus. Administration of certain b-blockers, such as atenolol, during pregnancy may result in small babies, although labetalol may be reasonably safe. Miscellaneous conditions There are a number of other conditions associated with hypertension where particular agents may be helpful. These are listed in Table 1.

Table 1: Conditions associated with hypertension and possible treatment Condition Drug Benign prostatic hypertrophy a-blockers Hyperthyroidism ß-blockers Migraine ß-blockers Atrial fibrillation ß-blockers   Verapamil, diltiazem Osteoporosis Diuretics

Combination antihypertensive therapy

Many patients will not have their blood pressure controlled by one drug alone. As most antihypertensive agents have fairly flat dose-response curves, using large doses of a single agent will produce significant increases in side effects without much further fall in blood pressure. The solution to this problem is to use a combination of two or more drugs. Effective combination therapy will use drugs with different primary modes of action. For example, b-blockers, which lower cardiac output, can cause bradycardia and tend to increase peripheral vascular resistance. However, these can be successfully combined with a calcium channel blocker, which causes vasodilatation and a reflex tachycardia. Diuretics are synergistic with most other agents, except the calcium channel blockers. There is evidence that the combination of a non-dihydropyridine calcium channel blocker and an ACE inhibitor reduces proteinuria more than either drug alone. The a-blockers can produce useful falls in blood pressure when combined with most other antihypertensive agents. In order to aid sensible prescribing, we have developed the “Birmingham Hypertension Square” for add-in drugs in the management of hypertension (Figure 1).25 The square may be approached from any corner, with first-line drugs chosen logically. The optimal second-line agents are immediately adjacent and indicated by the arrows.

Figure 1: The Birmingham “hypertension square” — developed as an aid to prescribing25

Dr Spencer is a research fellow and Dr Lip is consultant cardiologist and reader in medicine at the University department of medicine, City hospital, Birmingham