Spotlight on... hypertension

Our last 'spotlight on' of 2013 explores the symptoms, risks and treatments available for patients with hypertension.

Each month, our 'Spotlight on' series has looked into a different disease or disorder and provided us with details on the symptoms, risks and treatments available for patients. This month we're looking into hypertension.

Hypertension has been shown to be the number one individual cause of greatest burden of disease and mortality worldwide. pharmaphorum's Hannah Blake interviewed Dr Ernesto Schiffrin, President of the International Society of Hypertension (ISH), for more information.

Interview summary

HB: What is hypertension?

ES: Hypertension is the elevation of blood pressure above certain arbitrary numbers of systolic and diastolic blood pressure, above which risk of cardiovascular events increase. We know that already within the normotensive range that is within normal blood pressure, risk increases with progressive elevation of blood pressure, and that its risk starts to rise at about 115 mm Hg systolic blood pressure, and doubles every 20 mm Hg. Arbitrarily we define hypertension as blood pressure higher than 140/90 mm Hg in the office in adults. For children, there are tables that allow establishing the upper limits of normal.

Blood pressure is the result of the impact of the blood against the walls of arteries that distends them as the heart contracts during systole, or relaxes during diastole, and as this pressure increases above those upper limits of normal, 140/90, the vasculature suffers, is injured, becomes stiffer, thicker, and is more prone to atherosclerosis, and to blockages that lead to heart attacks, strokes, contribute to progression of kidney failure, and peripheral vascular disease that may lead to amputation of limbs. So these are some of the major consequences of high blood pressure: stroke, heart attacks, renal failure, peripheral vascular disease, and blindness due to compromise of the vasculature of the retina.

HB: Who is at risk from hypertension?

ES: About 20 to 40% of the adult population have hypertension. Very often when one or both parents of an individual have hypertension, the risk of being hypertensive increases dramatically, so there is a genetic component which is calculated to be about 40% of the causes that lead to elevated blood pressure. The environment contributes significantly, high salt intake is a major cause of elevated blood pressure, one usually mentions stress, but actually stress only causes transient elevation of blood pressure, and not sustained hypertension. Plus, obesity is a major cause of blood pressure elevation, and blood pressure is also elevated in most patients who have type 2 diabetes, generally but not always associated with obesity or overweight.

These are not only major causes, but also they are risk factors themselves for cardiovascular disease. In the case of obesity, if you take somebody who is 45 years old, is obese, and has blood pressure in the upper limits of normal, within four years this person will become hypertensive if they don't lose weight, according to the Framingham cohort of the United States. So weight loss is a critical aspect, which means physical exercise and diet, to which can be added cutting down on high salt intake, which are ways of lowering blood pressure non-pharmacologically, by lifestyle modification.

HB: Are there any symptoms to look out for?

ES: Hypertension is a rather silent disease. Sometimes headache may lead to the discovery of hypertension, but some people with very elevated blood pressure don't have headaches, and some people with relatively low blood pressures have headaches, and headaches are very frequent in the population. So even though headache may be a symptom, it is a rather generic symptom, and as I said very often hypertension is a silent disease. People have called it the silent killer; it's not a very nice way of putting it but may be quite true in fact.

HB: You've already mentioned weight loss, but are there any other ways you can prevent hypertension?

ES: Well essentially cutting down on high salt intake is important. There are recommendations from the International Society of Hypertension, from the World Hypertension League, from the United Nations, and the World Health Organisation, that recommend trying to keep salt intake close to five grams per day of sodium chloride, not more. That helps. Losing weight will prevent the rise in blood pressure, and the control of diabetes on the one hand, because diabetes is associated as I said very often with hypertension, but on the other hand control of blood pressure is very beneficial for diabetic people, since it is one of the main ways of reducing cardiovascular events associated with diabetes. But essentially the best ways to prevent hypertension are a healthy diet, exercise, weight loss, and lowering high salt intake.

Of course, any effort to reduce global cardiovascular risk must include avoiding or eliminating smoking. Smoking does not produce elevated blood pressure but it is a major cardiovascular risk factor, so any effort to control blood pressure has to be associated also with global cardiovascular risk reduction, including cessation of smoking.

HB: What treatments are available if you are a patient with hypertension?

ES: If you are diagnosed with hypertension, once you introduce lifestyle modification, which is a critical aspect with all the measures that I already mentioned, there are numerous classes of agents that are very effective in reducing blood pressure. This includes diuretics which eliminate salt- we know that most, if not all, the monogenic forms of genetic hypertension in humans are associated with defects in sodium elimination, and indeed eliminating sodium not only by cutting down on high salt intake, but also by the use of diuretics will contribute to lowering blood pressure. So this is one of the classes of drugs.

Another class, that are very important and very frequently used, are the agents that block the renin-angiotensin system, such as ACE inhibitors and angiotensin receptor blockers. There is also a new class of renin-angiotensin inhibitors, which are the renin inhibitors, they are much less used, there's only one agent, a relatively new one. And then there are calcium channel blockers of which there are different types.

These are the three main classes used alone or in combination. Beta blockers are also used, particularly in younger people, since there is evidence that beta blockers are less effective in older individuals, above age 50. However, there are compelling indications for the use of beta blockers such as patients with coronary artery disease, who require beta blockers, and so these are the main classes. There are also additional agents, such as mineralocorticoid receptor blockers like spironolactone and eplerenone which are used on top of the three classes of drugs that I mentioned at the beginning, particularly in cases of refractory or resistant hypertension. Finally, there are agents that act on the sympathetic nervous system, either alpha 2 agonists such as clonidine, some other related agents like alpha methyldopa, and alpha 1 adrenergic blockers, which are less used, particularly since a major study in antihypertensive therapy –the ALLHAT trial – showed that they could induce heart failure, and so these agents have been relegated to fifth line therapy, in addition to previous agents that I mentioned, when blood pressure is not yet controlled.

HB: In your opinion, how do you think pharma can better support patients with hypertension?

ES: I believe the problem is that for most drugs there's about a 60% response rate, and so we often use combination therapy, either adding drugs one after the other, for example starting with a renin-angiotensin blocker, adding a calcium channel blocker, then a diuretic, then a mineralocorticoid blocker. When blood pressure initially is already quite elevated we sometimes start directly with a combination therapy, for example renin-angiotensin blocker with a calcium blocker or a diuretic in the same pill.

Yet there are still around 15% or 20% of patients who cannot be controlled. In fact, when you look at the population globally, the control of blood pressure is quite dismal in many countries. In the most advanced countries, it may achieve about 50% control or even 60% control, but throughout the world, control of blood pressure is really dismal.

I believe that there is a place for new agents, and that pharma should make the effort of developing new agents. Pharma, on the one hand, needs to continue demonstrating the efficacy of the drugs that are already on the market, and of the combinations of drugs, and how they reduce major events, heart attacks, strokes, renal failure, and so on, and on the other hand work on discovering new targets for development of new agents. Some companies are in fact still interested, they understand that we need more drugs, because some patients have side effects with the drugs, whether real or not they report side effects. Many of the agents that I mentioned have very few side effects, they are very well tolerated, and yet many patients report side effects.

So there's always a place for new agents, which should in general be administered once a day, have a duration of action of about 24 hours, and be effective with few or no adverse side effects. So those are the two approaches that I believe pharma can help with.

Also, pharma could participate in educational programmes, to try to disseminate the idea of control of blood pressure, how important it is in reducing cardiovascular disease, and the burden that hypertension places on the healthcare system, because of its prevalence and its impact on cardiovascular events of importance, such as strokes and heart attacks and so on, and kidney failure. There are few things that are as dramatic and that so drastically affect quality of life as a stroke, and that are more costly from a human and a financial point of view, and that impose such a burden on the healthcare system. And so hypertension control is one of the best ways to reduce stroke, and therefore we should attempt to achieve greater control of blood pressure, which as I mentioned in many parts of the world is in fact very bad. I think that pharma should also attempt to help out in these areas of the world where access to medication is difficult, especially high quality medication.

HB: Finally, what do you think the future looks like for hypertension with regards to pharma and patients?

ES: I think that if we continue working hard and doing research, we will discover new targets. I myself am working on this. There are new opportunities as molecules are discovered. The whole area of microRNAs is one, and there is the attractive possibility of antagonising some of these if we discover that some might be interesting targets for hypertension control and to control vascular disease in high blood pressure. So as we develop this research in different countries, and in different research institutions we may be able to find new approaches for the treatment of high blood pressure. There are other approaches that are as well are being developed with new molecules.

On the other hand, an important aspect is compliance with medication, so ways of ensuring increased compliance also need to be developed. The research in hypertension that will offer new opportunities for patients goes from molecular and cellular, all the way to behavioural research that will ensure that patients take their medication regularly, don't forget to take their pills, and don't throw them out, which unfortunately does happen, fill their prescriptions, and as well follow the recommendations for lifestyle modification which go from maintaining a reasonable fitness, exercising, losing weight, cutting down on salt, stopping smoking, and leading a healthy lifestyle with an appropriate healthy diet - all these aspects require a lot of effort. There are few things as difficult as getting people to sustain weight loss, and so new approaches that will make this easier for patients, that will ensure the sustainability of weight loss, and healthy eating, decreasing salt in food, trying to make people eat natural foods rather than things out of a can or a package, all of these measures require research in order to ensure compliance by patients, which as I said is a major problem.

There are therefore many avenues for research and improvement in the treatment that we can offer both from the point of view of non-pharmacologic and pharmacologic therapy in order to improve the outcomes for our hypertensive patients. I think there's a lot of hope and that the future is bright.

HB: Thank you very much Dr Schiffrin.

About the interviewee:

Dr. Ernesto Schiffrin is Physician-in-Chief of the Jewish General Hospital and holds a Canada Research Chair in Hypertension and Vascular Research. He is Professor and Vice-Chair (Research), Department of Medicine, McGill University.

Dr. Schiffrin's research deals with mechanisms and treatment of high blood pressure, from molecules and cells to humans. He is author of more than 500 peer-reviewed publications, many book chapters and is editor of 3 published books, and 1 in preparation, on molecular and clinical aspects of vascular disease and hypertension.

Dr. Schiffrin has been President of the Canadian Hypertension Society (1991-92), Chair of the High Blood Pressure Research Council of the American Heart Association (2002-2004), President of the InterAmerican Society of Hypertension (2005-2007) and President of the Quebec Hypertension Society (2009-2011). Dr. Schiffrin has been Vice-President (2010-2012) and is now President of the International Society of Hypertension (2012-2014) and President of Hypertension Canada (2013-2014). Dr. Schiffrin has been Associate Editor of Hypertension (AHA journal) since 2003.

Dr. Schiffrin received the Senior Investigator Award of the Canadian Society of Internal Medicine in 2003 and the Distinguished Service Award of the Canadian Hypertension Society in 2004. He was elected Fellow of the Royal Society of Canada in 2006, and received the 2007 Irvine Page-Alva Bradley Lifetime Achievement Award of the High Blood Pressure Research Council of the American Heart Association and the 2010 Bjorn Folkow Award of the European Society of Hypertension. He was appointed Member of the Order of Canada (C.M.) in July 2010. He was awarded the 2011 Excellence Award in Hypertension Research of the American Heart Association, in September 2011. In February 2013 he was awarded the Queen Elizabeth II Diamond Jubilee Medal. He was named the 2013 American Society of Hypertension Distinguished Scientist and conferred the Robert Tigerstedt Award in May 2013. He received the Research Achievement Award of the Canadian Cardiovascular Society in October 2013.

How can we encourage patients to modify their lifestyles to prevent hypertension?