Prof. Denis Clement,
At the World Congress of Cardiology 2006 in Barcelona, the Council for Cardiology Practice organised for its members a number of presentations during a noon time Take-Home Message luncheon session. Together with last week’s e-journal, these messages will be presented in this and later issues of the e-journal. In respect to hypertension, there is good news and there is bad news. Blood pressure control is more efficient if seen as part of total cardiovascular risk yet the effective means we have to combat hypertension are still underused.
To better control the risks linked to hypertension, it is recommended to see it as an integral part of total cardiovascular risk. This suggestion comes from the guidelines of our society (1). Even at high normal pressure, total cardiovascular risk can be severely elevated when other risk factors are added. Such an augmentation can be expressed as a number because it also quantitatively depends on the numerical value of blood cholesterol, the number of cigarettes smoked and so on. In table 1, you may see the results that come out of such calculations. Take for example a patient with a so-called high-normal blood pressure (130/85 mm Hg). If there are, on top of blood pressure, a few other risk factors in the calculation of his or her total cardiovascular risk, one quickly comes to what is called a "high added risk". Compare this patient’s results to the patient whose pressure is 180/110, this second patient reaches the same level of risk even without any other risk factor to account for.
Table 1 : Stratification of Risk to quantify prognosis.
In practice, physicians often will behave differently when faced with these two patients. The patient with 180/110 will most likely receive immediate antihypertensive drugs while the other will often have his or her treatment postponed because the figure does not "look" so bad! Yet, both patients' total cardiovascular risk is in the same range. One can go ahead and realise what this means at the level of a whole population as the prevalence of the patient type 130/80 mm Hg. is much higher!
Seeing the problem in that way provides the physician with many new possibilities for controlling risk, and more particularly the risk coming from high blood pressure. Indeed, the risk of hypertension can significantly be decreased by lowering the weight of other risk factors such as cholesterol, blood glucose etc. This new approach is often helpful in patients who present a risk factor that is hard to control. A typical example is the hypertensive patient in whom it is impossible to come to target blood pressure because of side effects, insufficient compliance for the drugs etc.
This approach resulting from the measurement of total cardiovascular risk- which is to lower the weight of other risk factors such as cholesterol, blood glucose etc-. is very useful and appropriate when total cardiovascular risk is severely elevated. Peripheral artery disease (PAD) causes such en elevation.
Several presentations in Barcelona have again, focused attention on PAD, a condition that is still underestimated by cardiologists. The risk of PAD is at least as high as stable angina pectoris (2) and maybe higher according to the recently presented REACH data. Recent information shows that PAD’s prevalence is also quite high in women above 50 years of age and these patients often present signs of ischemia that are very difficult to manage.
There are no arguments that some classes of antihypertensive drugs would do better than others in these PAD patients. Still, there is some argumentation that ACE inhibitors may better control symptoms of intermittent claudication and therefore allow for a better controlled prognosis.
In PAD patients with hypertension, beyond the discussion of what drug should be used, is the problem of target blood pressure. Cardiologists increasingly realise that PAD carries a risk close to that of diabetes. Therefore, it would be logical that target blood In PAD patients with hypertension should no longer be 140/90 mm Hg as for regular hypertension but rather 130/80 as for diabetic patients. Unfortunately, there are at present not enough good studies to prove this statement;
Nevertheless, as the risk of PAD is so much underestimated and the disease underdiagnosed, too often, control of total cardiovascular risk is forgotten in these patients. It is generally accepted that such risk can be decreased by administrating antiplatelet drugs (aspirine or clopidogrel), ACE inhibitors and statins on top of the antihypertensive treatment. All means to improve drug compliance should therefore be used to keep PAD patients on the safe way!
Patients with cerebral artery disease (CVD) are the other category of often underdiagnosed and undertreated patients. There is a continuous relationship between blood pressure and cerebrovascular events. This relationship is sharper when other risk are added, joining the above mentioned principles on total cardiovascular risk. Again, the three drugs classes that control total risk should be administered (antiplatelet durgs, ACE inhibitors and statins). Concerning hypertension, there are no strong arguments that one drug class does much better than another. Older studies had emphasised the value of calcium antagonists but the advice of the antihypertensive Trialist’s are not very conclusive in this respect. Two recent studies have investigated the role of antihypertensive treatment in the secondary prevention (i.e. after having suffered a cerebrovascular event). In the Progress study (3) Perindopril (eventually associated to Indapamide) was compared to control in more than 6000 patients. There was significant decrease in stroke and in major CV events with active treatment. Best results were seen when blood pressure control was optimal. In the Moses study (4) Eprosartan was compared to Nitrendipine in 1405 patients; the number of cerebral events was significantly better controlled with Eprosartan than with Nitrendipine; still the difference was not very large. The good news is thus that effective control of blood pressure on top of the other risk factors results in a significant improvement of prognosis of these patients, both in primary as well as in secondary prevention. However, compliance to the drug treatment needs careful follow up (see below, the bad news).
There are several new classes coming up to better control hypertension. (table 2). The renin inhibitors are a quite interesting class blocking the renin-angiotensin axis at the level of renin activity. One drug, Aliskiren, has a quite specific action causing a significant blood pressure decrease which is long lasting; also the safety profile looks favorable. The Urotensin II receptor blockers inhibit the effect of the strong vasoconstrictor urotensin. The vasodilatation results in blood pressure decrease which is attractive but the effect seems to be variable from patient to patient. Rho-kinase inhibitors are in the middle of research at the cellular level as they can interfere with the mechanism that lead to vasoconstriction. There still is a lot of interest in other drugs of the class of the mineralocorticoid receptor antagonists. The oldest drug, Spironolactone, does quite well but has in some patients, a number of unpleasant side effects. Therefore another dug, Eplerenone, is being investigated causing a blood pressure decrease similar to Losartan, but less gynecomastia than with Spironolactone. Also other drugs in this class are being investigated such as the Aldosterone synthase inhibitors. Finally, the endothelin antagonists continue to be good candidates as antihypertensives; the best know drug (bosentan) is well known in the treatment of pulmonary hypertension but another drug in this class (Darusentan) could present us with new possibilities in cases of resistant systemic hypertension.
Table 2. New drugs in hypertension.New antihypertensive drugs classes
Blood pressure, worldwide, is still insufficiently controlled. Several data coming from EuroAspire and EuroAction have clearly shown that we have not made any significant progress in blood pressure control in the last 10-15 years. There has been a quite clear improvement in the 1980’s but not much has happened for the better since. The problems lie at the level of the detection of hypertension itself but they continue onwards: many patients have started treatment at some time but do not continue and are lost for follow up. EuroAspire data show that even after having suffered a severe event, control of risk factors and hypertension particularly, is far from ideal. Target blood pressure is rarely attained and this is at least as bad in patients in whom risk is particularly severe as in diabetes. It is most likely that patients are not instructed enough on the risks of hypertension. Perhaps physicians themselves should be re-instructed on this issue as well. Many let themselves be guided by the idea that high blood pressure at consultation is a white coat effect und thus, do not estimate the “real” blood pressure level. If this indeed the case, ambulatory or home blood pressure should be recorded but even these techniques, which are very helpful to confirm the level of pressure and to estimate prognosis(5), are underused.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.
This issue of insufficient blood pressure control, is one of the most important ones to reflect upon; research on diagnosis and on newer therapeutic means are largely useless if they are not applied in real practice and continued throughout. New programs should be set up on the risks of hypertension and on the many, very effective means we have to combat this problem. We just have to use these means…
1. 2003 Guidelines for the management of Hypertension.J.Hypertension: 2003: 21: 1011-1053 2. Clement DL, Boccalon H, Dormandy J, Durand-Zaleski I, Fowkes G, Brown T. A clinical approach to the management of the patient with coronary (Co) and/or carotid (Ca) artery disease who presents with leg ischaemia (Lis). Int Angiol. 2000 Jun;19(2):97-125 3. PROGRESS Collaborative Study Group. Randomised trial of Perindopril based blood pressure-lowered regimen among 6108 individuals with previous Stroke or transient ischaemic attack. Lancet: 2001:358:1033-1041
4. Schrader J, Luders S, Kulschewski A, Hammersen F, Plate K, Berger J, Zidek W, Dominiak P, Diener HC; MOSES Study Group. Morbidity and Mortality After Stroke, Eprosartan Compared with Nitrendipine for Secondary Prevention: principal results of a prospective randomized controlled study (MOSES). Stroke. 2005 Jun;36(6):1218-26. 5. Clement DL, De Buyzere ML, De Bacquer DA, de Leeuw P, Duprez DA, Fagard RH, Gheeraert PJ, Missault LH, Braun JJ, Six RO, Van Der Niepen P, O’Brien E. Prognostic value of ambulatory blood pressure recordings in patients with treated hypertension. NEJM 2003; 2407-2415.
Prof. D.L. Clement Ghent, Belgium Nucleus member of the Council for Cardiology Practice. Past-president of the WG on Hypertension and the Heart and the WG on Peripheral Circulation.
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