Why worry about high blood pressure?

29.4.14: Listen to blood pressure specialist Donald Singer and pharmacist Ejaz Cheema in discussion with Annie Othen on BBC radio about blood pressure, knowing your numbers, tips on blood pressure measurement, why treatment is important, and how doctors, nurses and pharmacists can help to keep people with high blood pressure as healthy as possible.

High blood pressure is a very common preventable cause of stroke, heart attack and other serious diseases. These complications may at best cause disability and are major causes of preventable premature death in the UK and around the world.

For the public in general, the lower the blood pressure the better: most blood pressure-related heart attacks and strokes occur at blood pressure levels within what many still consider to be normal blood pressure.

A healthy lifestyle will help to keep blood pressure and other cardiovascular risk factors in check.  Keeping weight in check, regular exercise, minimising salt intake and moderation in alcohol, as well as eating healthy foods rich in fruit and vegetables all help, as does avoiding or stopping smoking.

For people with raised blood pressure, tests are important to rule out underlying causes and to identify other cardiovascular risk factors.

Blood pressure treatment is well-established as effective in helping to prevent or reduce severity of heart attack, stroke and other serious medical problems. However  blood pressure is still poorly controlled in many patients even in the most developed healthcare systems.

One of several reasons for poor blood pressure control is that many patients find it difficult to keep taking their tablets. Surprisingly, in people newly diagnosed with high blood pressure, as many as half may have stopped their tablets by 12 months.

It is as important to understand and address reasons for poor patient adherence with their medicines. These include not being sure of why blood pressure is important, reasons for choice of medicines, and concerns about possible or actual side effects of tablets.

Other contributory factors includes failure of prescribers to follow established national guidelines for choice of tablets and how they should be used singly or in combination. This risks exposing patients to avoidable side effects without achieving effective lowering of blood pressure.

An important element in approaches to improving adherence to blood pressure medicines is continuing education of health professionals and patients about high blood pressure and its treatment. Doctors, nurses and pharmacists can all play important roles in this.

Cutting nerves in the neck to treat high blood pressure?

According to an experimental study published in Nature Communications, severing key nerves in the

neck may provide a new option for lowering high blood pressure.

Considering new approaches to treating high blood pressure (hypertension) is crucial. High blood pressure is a very common and important cause of disease and death resulting from problems with the heart, and with the blood vessels in the body and brain.

Treatment to lower high blood pressure is supposed to continue for decades. However, even by 12 months after the starting treatment, around 50% of patients are not taking their tablets regularly, if at all.


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International Hypertension Society Congress in Sydney, 2012

Darling Harbour

@HealthMed An excellent setting for the 2012 ISH Congress - the Sydney Congress Centre, overlooking Darling Harbour in the centre of the harbour city of Sydney - amid a weekend of euphoria for sporting enthusiasts, after close success for the Sydney Swans over Hawthorn in the Footy (AFL) Grand Final, following by a win for the Melbourne Storm over the Canterbury Bulldogs in the NRL Grand Final - and the astonishing win by Europe in the Ryder Cup ...

At least a few of the almost 2000 international delegates appeared tempted into the city by the Spring sunshine.

Some of the early Congress highlights:

- Jeffrey Moore, Monash University, discussing targeting innate immunity to treat vascular hypertension
- Ernesto Schiffrin, Montreal, on immune mediation of angiotensin II induced vascular pathology
- Steve Vatner, New Jersey Medical School, giving a sceptical view of the role of apoptosis in cardiomyopathy and heart failure

NMM, Darling Harbour

- Eric Olson, University of Texas Southwestern Medical Center on microRNA control of cardiovascular disease, including the role of microRNAs in cardiac regeneration, cardiac Med13 as an enhancer of systemic energy expenditure and cardiac specific deletion of Med13 causing severe obesity, and antimiR-208 as a potential treatment to prevent obesity and features of the metabolic syndrome
- Rick Lifton, Yale,  on outcomes of $650 per person human genome scanning, from causes of adrenal adenomas to new genetic causes of renal mishandling of electrolyte and water balance.
- and many excellent research posters from basic science reports to clinical applications of research ...

Opium and mortality

@HealthMed Opium is widely used internationally. A study from Iran just published in the British Medical Journal now reports almost doubling of mortality rates in regular users of opium.

Here are my comments to the Science Media Centre on this study:

"The key message in this prospective study on opiates is of interest to pharmacologists, health professionals and members of the public: use of recreational opium, whether raw or modified, smoked or swallowed, appears associated with increased risk of death from a wide range of diseases, including circulatory and respiratory disorders, and cancer.

"However the results need to be interpreted with caution. This work is from north-east Iran and may not be typical for other ethnically or genetically different individuals. The authors note that they cannot be sure whether the relationship is causative. And oddly, risks from opiates did not appear to be amplified in people with high blood pressure, smokers or diabetics, raising some questions about the accuracy of clinical data collection."

Although some commentators have linked findings of this study to use of medically prescribed or over the counter opiates, there are too many confounders for that to be a reasonable extrapolation from the BMJ study. Nonetheless the general principle remains that medicines should only be used when clinically indicated.

See more about the study and related comments on the New Zealand Science Media Centre site.

Companion diagnostics - a new concept for safer medicines?

@HealthMed Diagnostics can be used in several ways: to establish the nature, subtype and severity of disease; to monitor wanted response to treatment with lifestyle, drugs and/or devices; to monitor for disease progression and for adverse effects of treatment. The term 'companion diagnostics' describes coupling diagnostic imaging or laboratory investigations with selection and monitoring of treatment. Although a logical idea, its use in the medical setting appears surprisingly recent.

In the late and 1980s and 1990s, reports of the use of combination diagnostics appear largely applying to veterinary and dental practice.

The partner term 'companion therapeutics' was used in a 2003 commentary on the FDA  "Draft Guidance for Industry: Pharmacogenomic Data Submission" issued on November 3, 2003, which noted that the [pharmaceutical and biotech] 'industry is now expected to accelerate its development of diagnostics and companion therapeutics towards the goal of personalized medicine'. Implicit in this evolution of a personalised approached to medicines is the recognition that diagnostics will not necessarily identify that a given patient may have a safe or effective treatment flagged as the result of testing.

An early example of a pharmacogenetic companion diagnostic is the UGT1A1 molecular assay for in vitro diagnostic use. This pharmacogenetic test was approved in 2005 by the FDA for use as a companion diagnostic to a specific drug therapy. The test was to be used to identify mutations in this gene in patients who may as a result be at increased risk of adverse reaction to the anti-cancer drug irinotecan. 

2006 and 2007 discussion of companion diagnostics pointed both to more efficient patient selection for clinical trials and a more profitable approach for drug developers. 

Current descriptions use narrower definitions of companion diagnostics as referring to tests to 'identify and detect genetic, protein, or gene expression markers to predict whether a drug works or causes adverse effect in patients'. However there is a long history of coupling tests with treatment choice and refinement, in every therapeutic area from cardiovascular disorders such as hypertension and raised cholesterol, to anaemia and treatment of lung, gastro-intestinal, renal and neurological disease.

To date there are only 75 publications in the PubMed research database with companion diagnostics as a key term, with a typical recent example from August 2011 in Nature Reviews on Clinical Oncology by La Thangue and Kerr applied to cancer chemotherapy: Predictive biomarkers: a paradigm shift towards personalized cancer medicine.

© DRJ Singer 

Why have a National Blood Pressure Week?

 In the UK, over 1,500 venues are offering free blood pressure checks during National Blood Pressure Week (12-18 September 2011). Why all that effort?   High blood pressure is a major preventable and treatable risk factor for serious heart diseases and stroke syndromes throughout the world. And even at the age of 20 around one in 20 people may already have high blood pressure, increasing to around 1 in 2 people by the age of 70.

An annual blood pressure week provides an important focus to remind the public and health professionals about risks of high blood pressure, how to prevent it, measure it accurately and use lifestyle and drugs in people in whom blood pressure is too high.

Blood pressure should be as low as possible, with, for adults, the upper level, when the heart has contracted, below 140mmHg and the lower level below 90mmHg, when the heart is relaxed between heartbeats. These thresholds should be much lower in people at increased risk of blood pressure complications, such as diabetics and people with kidney disease.

Provided people are otherwise healthy, the ideal blood pressure is now considered by international experts for the upper value to below 120, the lower below 80, recorded as ‘below 120/80mmHg’.

It is very important that patients help by following a healthy lifestyle. This is both helpful to prevent high blood pressure, and for patients with hypertension, to reduce its severity. People should aim for a healthy weight, using fresh foods as far as possible, keep salt intake low, and alcohol intake within healthy limits, be active and have regular good sleep.

This year it is timely the UK’s National Blood Pressure Week comes just after the launch of important new blood pressure guidelines prepared by the National Institute for Health and Clinical Excellence (NICE) advised by experts from the British Hypertension Society (BHS).

The NICE guidelines contain new advice on blood pressure measurement, including involvement of patients in their own management, supported by home blood pressure readings.

It is of course very important that any blood pressure monitor, whether for clinical or home use, should be accurate. A helpful list of accurate devices is on the British Hypertension Society's website.’

If you have high blood pressure, you should make sure that your doctor knows about any over the counter tablets or herbal remedies you are taking, as these can interfere with the actions of blood pressure tablets.

There are now seven major types of blood pressure treatments. For best blood pressure control, prescribers need to the right drug options for the right kind of patient, taking into account, for example, age, ethnicity and potential risks in pregnancy. If single drugs are not sufficient to control blood pressure, the NICE guidelines provide advice on which drug combinations are best to use.

Useful websites:
British Hypertension Society – includes information on which blood pressure monitors are accurate  http://www.bhsoc.org
Blood Pressure Association – includes a list of venues for free blood pressure checks http://www.bpassoc.org.uk/
NICE guidance on hypertension for patients and carers: http://guidance.nice.org.uk/CG127/PublicInfo/pdf/English

Networks and personalized medicine for better drugs?

For more on this theme see 
- article with Andrew Marsh in the inaugural March 2012 issue of Health Policy and Technology
- article in the October 2011 issue of Public Service Review: Science and Technology Review.  

For many individual patients treatments may not exist, may not be very effective, or may result in unpleasant adverse effects. How can prescribers improve drug selection andreduce the harmful effects of medicines? Are there better ways to develop drugs for patients who are difficult to treat?  And what can we do to improve poor adherence to medicines? These elements underpin ‘personalized medicine’, in current use the concept that by considering differences among patients in genetics, disease burden and other factors, more effective and safer drugs can be developed. Personalizing medicine is a path to better disease prevention and control where limited treatment options exist, such as for many cancers, resistant infections and dementia syndromes, and better drug development for new medical challenges. These concepts have in recent years attracted interest from the Royal Society, the Nuffield Council on Bioethics and cognate international institutions.

It is clear that there needs to be consistent investment and support from policy makers and regulators to develop and sustain the academic and industry pharmacology expertise and activity needed for the long-term success of a personalized medicine strategy, so that we can continue to be able to improve the health of the public and individual patients.

NICE is an international leader in developing evidence-based treatment guidelines. Its reports increasingly recognize the need to refine drug choice based on patient characteristics. For example, updated national hypertension guidelines released in August 2011 advise drug selection guided by age, gender, ethnicity, and monitoring, with treatment modified depending on clinical response. NICE also recognizes the need for research on ways, tailored to patient preference, to improve long-term adherence to drug treatment.

Pharmacologists are developing two complementary approaches aimed at achieving “precision medicine” in as many patients as possible: better drug discovery combined with high definition biomarkers for drug selection and monitoring. Network pharmacology brings together sophisticated databases of genetic mechanisms for disease, pharmacological pathways, candidate drugs, and population data describing important variants among individuals in drug handling and responsiveness.  These methods also allow ways to find previously unexpected “off-target” actions of existing or new drugs, which may accelerate discovery of new treatments for serious diseases.

Diagnostic methods are increasingly being used to improve drug selection for individual patients. For example growth tyrosine kinase receptors can be blocked using the biological agent imatinib to treat particular patterns of Philadelphia chromosome-positive chronic myeloid leukaemia, and rare gastro-intestinal tumours. Understanding genes and drugs that influence enzymes that modify drugs in the body, improves accuracy in defining patients who will not respond to a given medicine, or may develop adverse effects.  For example, to minimize risk of serious harm, pharmacogenetic testing is recommended for variability in a specific liver enzyme before deciding whether or not to prescribe the anti-HIV drug abacavir. This knowledge also allows better prediction of a patient’s risk of harm from interactions between treatments, based on recognition of medicines and other remedies that interfere with how drugs are cleared by the body. 

See my previous blogs on 
- preventing adverse drug reactions
- new UK guidelines on managing high blood pressure