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Published on 1 January 2004

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Progress in hypertension diagnosis and treatment

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Denis L Clement
MD PhD
Professor Emeritus of Cardiology
University Hospital Gent
Belgium

Until now a diagnosis of hypertension was made by measuring blood pressure during the consultation. However, this has the potential to create mistakes in diagnosis, with the main problem being that blood pressure is not a constant entity but changes from moment to moment throughout the day.

Blood pressure has to change as part of the adaptation of the body to circumstances in which the person finds themselves; when the body is at rest, blood pressure will be lower than during activity or when the body is in a high-stress situation.

Everyone in the hypertension field was aware of this problem, but it has been difficult to find good alternatives. Advances in monitoring occurred in several stages:

  • Stage one – blood pressure was measured automatically by a machine, without the presence of doctors and nurses in the room. However, the patient had to remain in the room and be connected to the machine the whole time.
  • Stage two – a number of systems were developed whereby the patients inflates the cuff themselves and a machine records the result automatically. With such monitoring systems, patients can move into their normal environment. Readings can be recorded throughout the day, but results can vary according to how well the patient inflates the cuff, and no measurements can be taken at night. There is also the problem of patients forgetting to take the measurement.
  • Stage three – fully automated systems were developed where the patient is fitted with cuff in the morning before going about their normal day, with blood pressure measurements being taken automatically every 30 minutes over a

24- or 48-hour period, even during sleep. This works relatively well, avoiding the possibility of missed measurements, but the inflation of the cuff at regular intervals is still a bit unpleasant and disruptive for patients.

Ambulatory blood pressure readings taken over 24 hours reveal significant variations in blood pressure throughout the day. A pattern is revealed:

  • At night, blood pressure is quite low.
  • It increases quite quickly early in morning as soon as you get up.
  • During the late morning/early afternoon, blood pressure goes down again.
  • Blood pressure rises in the late afternoon at 4pm or so, then falls again during evening and at night.

Blood pressure measurements are influenced both by this daily pattern and by the different situations in which we find ourselves during the day.

As soon as it was realised that blood pressure is a curve rather than a number, the question that followed was which measure we should use to make the diagnosis – a single measurement taken at consultation and repeated on two or three occasions, or a series of readings collected over a 24-hour period. To find out the answer, a study was carried out involving 2,000 treated hypertension patients at centres across Europe, who underwent blood pressure readings made at consultation and over 24 hours at the start of the study, and who were followed up over a five-year period.(1) All cardiovascular events (eg, myocardial infarction, heart failure, stroke) were recorded on specially validated forms, then statistically correlated with the blood pressure measurements taken at the start of the experiment, with 24-hour blood pressure readings made at the same time. Analysis revealed a difference of at least 10mmHg between the two. These findings demonstrated the need for redefinition of ambulatory blood pressure levels and reworking of target blood pressures and limits.

Following these patients over five years clearly illustrated that hypertension is a dangerous disease, as it correlated closely with subsequent cardiovascular events – those with the highest readings experiencing the greatest number of events.

Despite the fact that all these patients were being treated according to the accepted guidelines, they were still not reaching target levels and continued to experience coronary events, something that has been revealed by previous studies. One is left wondering what blood pressure levels are like in patients who are not receiving optimal care as part of a well-controlled study.

A breakdown of the cardiovascular events that occurred over the trial period revealed that most events took place in patients with the highest pressure levels, a little more in males and clearly more in those with most other risk factors.

In answer to the question that formed the main purpose of the study, cardiovascular events correlate best with 24-hour ambulatory measurements; from this it is possible to infer that an ambulatory reading is the most accurate method of predicting the risk to the patient over the coming years.

Further analysis of the data also revealed a surprising new conclusion. It is well established that a certain proportion of patients experience so-called “white-coat hypertension” (ie, their blood pressure reading at consultation is much higher than it would be normally), so unless they undergo 24-hour monitoring they may be receiving unnecessary treatment. What wasn’t previously known was that up to 20–25% of patients whose blood pressure appears normal at consultation (140/90mm Hg or lower) actually have unacceptably high blood pressure as revealed by 24-hour ambulatory monitoring – a process known as reverse hypertension.

Under normal circumstances, these patients would have been accepted as being well controlled – the doctor had done the job and the patient was not at risk. Those patients who seemed to be well controlled at consultation may be at high risk because their ambulatory pressure is high. This is an important notion – when following up patients on hypertension treatment, an ambulatory check must be carried out from from time to time to monitor continuing risk. While the ideal frequency of ambulatory monitoring is not yet known, a once- yearly check is probably adequate, unless something clinically raises suspicion that there is a problem.

From the results of this study, two important conclusions can be reached. The definition of high blood pressure needs to be rethought because 24-hour ambulatory recording clearly correlates better with long-term prognosis. When following treated hypertension patients over the longer term, 24-hour monitoring should be done from time to time, because even in apparently well-controlled patients a certain fraction are at high risk because their ambulatory blood pressure is higher than that measured at consultation.(1)

Trends in hypertension management
Until the publication of new hypertension management guidelines in June,(2) many doctors viewed the management of cardiovascular risk in the light of their own particular area of interest: hypertension specialists looked at blood pressure only, those with an interest in lipids looked at lipids only, and those concerned with metabolism focused on weight, glucose and so on.

The guidelines promote a more holistic approach to cardiovascular risk. Management should begin by compiling all the cardiovascular risk factors, such as high blood pressure, high lipids and glucose, overweight and cigarette smoking, to calculate a global risk score for the individual patient. The total risk score incorporates damage to target organs that the patient has already experienced, such as left ventricular hypertrophy (LVH; an increase in wall thickness of the left ventricle of the heart) and changes in the blood vessels, kidneys and circulation to the brain. It is important to include existing organ damage as this is a risk factor in itself (see Figure 1).

[[HPE12_fig1_60]]

Calculation of global risk is not just academic – management of the different risk factors will vary depending on whether total risk is high or low. For example, the urgency of treating someone with moderately high blood pressure (eg, 150/95ml Hg) but a low global risk score is much lower than a patient with the same blood pressure but a higher risk score. The philosophy of treating blood pressure, lipid levels and so on will be conditioned by the total risk score established before treatment.

In daily practice, most patients have blood pressure values that fall into a grey area of 150–160/90–95mmHg – it is rare to see very high blood pressure values in Western Europe today. The approach to management taken will depend on the totality of risk in each individual patient.

Treatment
Management always starts with lifestyle modification: some exercise, quitting smoking, trying to control weight, and reducing salt and saturated fat in the diet. This should not mean that life becomes unpleasant. It is unrealistic to tell patients they should drastically alter their lifestyle – instead they should adjust their current way of living to more acceptable levels.

If this doesn’t bring blood pressure down to target values, treatment with antihypertensive drugs can be commenced. According to the 2003 guidelines, all available drugs can be regarded as firstline. Previously diuretics or beta-blockers were regarded as the firstline treatment option, as they are older (so a lot is known about them) and cheaper. Many doctors will still start with these two classes, but there are situations where they will choose another drug because they feel it is more appropriate. The final choice should depend on the characteristics of the patient.
As a general rule:

  • Diuretics are good for patients overloaded with fluids, such as oedema in the legs (due to some degree of heart failure). They are still the cheapest form of treatment.
  • beta-blockers are given to patients under high sympathetic tone, where the nervous system increases the heart rate and alertness of the patient. This is often the case in younger patients where life is placing a lot of stress on them.
  • ACE inhibitors are given to those with LVH. It is well established that ACE inhibitors are very good at decreasing hypertrophy.
  • Angiotensin-II antagonists (AIIAs) are an excellent alternative for patients who are having trouble with ACE inhibitor side-effects (they can cause quite an unpleasant cough). They are also useful for patients with kidney alterations in addition to hypertension.
  • Calcium antagonists are good where the patient has narrowing of some of their blood vessels.
  • The alpha-1 receptor blockers are excellent in patients where, besides hypertension, the patient has prostate problems – as is the case in many older men.
  • Centrally acting antihypertensive drugs act directly on the central nervous system (CNS). They hadn’t been used for a number of years because they were associated with unpleasant side-effects. Recently, however, new drugs in this class have been developed, such as moxonidine, which is now on the market in many European countries. It reduces CNS activity, and when given at night improves sleep. It is quite a soft drug – ie, works slowly – and is therefore good for treating hypertension in elderly people where a more gradual effect is beneficial. It also increases sensitivity to insulin.

As a final point, new thinking is pointing to the benefits of associating two antihypertensive drug classes at once, commencing with both drugs at a low dose. Very often one drug is not enough to get blood pressure low enough and adding a second drug will do the job. Giving two drugs at low doses reduces side-effects and improves efficacy. The choice of which two to combine is fairly open, with low-dose diuretic plus ACE inhibitor or calcium antagonist plus b-blocker being popular choices.

References

  1. Clement DL, De Buyzere ML, De Bacquer DA, et al. Prognostic value of ambulatory blood pressure recordings in patients with treated hypertension. N Engl J Med 2003; 348:2377-8.
  2. 2003 European Society of Hypertension–European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003;21:1011-53.


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