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Prof David J Webb

High Blood Pressure Foundation 15th Annual Report 2005

Research Report by Professor David J Webb, 2005

 

Happily, we now have a wealth of good medicines for the treatment of mild to moderate hypertension. These are all simple to take (once daily), lower blood pressure effectively for as long as they are taken, and cause relatively few side effects. In addition, good alternatives are usually available when side effects occur. We are now also increasingly aware, from very large clinical trials, that while there may be subtle differences between the medicines, and some may suit one person better than another, the key driver of cardiovascular benefit is the effect these drugs have in lowering blood pressure. For this reason, we need to maintain a major focus within the High Blood Pressure Foundation on awareness of high blood pressure, its early detection, and finding persuasive reasons to stick with the medicines once started.

 

A key aim for those advising and managing patients with high blood pressure is to calculate cardiovascular risk and target treatment to those individuals who can be expected to derive a reasonable benefit from starting treatment. In this regard, work done by Dr Rupert Payne for the Cardiovascular Risk Clinic at the Western General Hospital, and available on the web (http://cvrisk.mvm.ed.ac.uk/calculator.htm), has been extremely valuable. He has developed a new improved version of an earlier cardiovascular risk calculator that now generates easy-to-read graphs based on the Joint British Societies cardiovascular risk prediction charts. Input of age, gender and smoking status, as well as blood pressure and cholesterol levels, can be used to achieve an estimate of 10-year cardiovascular risk (primarily of a stroke or heart attack). This new facility should be a great help in discussion between patients and doctors at the Cardiovascular Risk clinic, as well as for any general practitioners who wish to access this information and use it in their discussions with patients. Once high blood pressure has been detected a central issue is whether treatment will provide benefit, and to what extent. We believe that access to this sort of user-friendly new technology will be of real benefit to both patients and doctors.

 

Areas where we have more difficulty with high blood pressure are in the rarer situation of trying to get down to a target blood pressure in patients with so-called ‘resistant hypertension’ (failing to respond to 3 medicines), and those with renal disease (including patients with diabetes). These are a relatively small minority of patients, but very important because they are at a particularly high risk of strokes and heart attacks. This work has taken two general directions. The first is a clinical trial focused on resistant hypertension in people who have no particular reason to have a failure of response to the commonly used medicines. Here, Dr James Oliver at the Western General Hospital is studying the benefits of add-on treatment with a combination of a nitrate (often used to treat anginal heart pain, but not normally used for high blood pressure) and a phosphodiesterase inhibitor (usually a weak dilator of blood vessels and so a poor blood pressure lowering treatment). Our department has already published work showing that this combined approach of nitrate and phosphodiesterase inhibitor powerfully lowers blood pressure in health people and patients with angina. The natural extension of this work should soon show us whether this approach will be helpful to patients with resistant hypertension. The second clinical trial is focused on patients with renal (kidney) disease. Here, in a series of studies led by Dr Neeraj Dhaun, in collaboration with Dr Jane Goddard, Consultant Renal Physician at the Royal Infirmary of Edinburgh, we are studying the effects of a new approach to blood pressure in this group of patients. In particular, endothelin, a hormone that constricts blood vessels and powerfully increases blood pressure, seems to be overactive in this situation, and especially sensitive to a high salt intake, so medicines that act as antagonists to endothelin, and block its actions may be helpful here.  Dr Dhaun has already completed work showing that endothelin antagonists lower blood pressure in healthy people and patients with renal disease, and Dr Goddard, has shown substantial benefits on blood pressure of a single dose of an endothelin antagonist. Dr Dhaun’s next studies will address the link to salt intake, show how well endothelin antagonists work alongside current treatments used in this situation. If the results are favourable, this should progress shortly into a clinical trial on blood pressure lowering. Also, if the work of Drs Oliver and Dhaun shows promise, either or both of these strategies could fairly rapidly translate into clinical benefits for patients.

 

Work continues on understanding the early life origins of high blood pressure and elevated cardiovascular risk in childhood and adolescence. We are currently collaborating with Dr Louise Bath at the Royal Hospital for Sick Children, to examine the effects of body weight and distribution, diabetes and other emerging risk factors. We are very grateful to the families that have helped in this work.

 

 

David J Webb