Tag Archives: MRC

Does treating high blood pressure do any good?

 

Although I am most interested in the medical madness surrounding cholesterol lowering and statins, I have long been interested in the parallel ‘Looking Glass’ world of blood pressure lowering. During a recent on-line discussion, someone recently sent me a link to study from two or three years ago which re-ignited my interest in this area.

‘A new review has found that lowering blood pressure below the “standard” target of 140/90 mm Hg is not beneficial in terms of reducing mortality or morbidity1.’ July 2009

It confirmed, or re-confirmed, what I have long believed to be true. Unless the blood pressure is very high, lowering it seems to be an exercise in ‘sweeping a symptom under the carpet,’ rather than doing anything remotely useful. However, before discussing the management of raised blood pressure in more detail, I need to establish a little context.

The average blood pressure of an adult is around 120/70mmHg. The 120 ‘systolic’ figure represents the highest pressure reached. This happens just after the heart has finished contracting. The 70 ‘diastolic’ figure represents the lowest pressure, occurring just before the heart contracts again (there is no time for it to drop all the way down to zero).

There is no doubt that, if the pressure is very high, say 200/120, that this is associated with a greatly increased risk of stroke, heart failure and other form of cardiovascular disease. No-one disagrees with this, not even me.

There is also no argument that lowering an extremely high blood pressure can be lifesaving. But, or perhaps there are many different buts here. Things are far less straightforward when it comes to a moderately raised blood pressure.

The first question to ask is. What exactly are we ‘treating’ when we lower it? A raised blood pressure is not a disease. It is not even symptom of a disease; because a raised blood pressure does not cause any symptoms unless it is extremely high. A raised blood pressure is simply a sign, or a measurement.

What is it a sign of? It is a sign that your heart is pumping so hard that the blood pressure is raised above the ‘normal’ level. Why would the heart pump too hard? It is statement of the obvious to say that it cannot just happen for no reason at all.

In some cases, an underlying cause can be found. If you have a narrow renal (kidney) artery, for example, this reduces blood supply to the kidney. The kidney therefore believes that the blood pressure must be too low, and it releases hormones designed to raise the blood pressure. Cause and effect.

In a case like this, you can do an operation to widen the renal artery, the blood flow to the kidney increases, and the blood pressure normalises. In around five per cent of cases of high blood pressure a cause, such a renal artery stenosis, can be found. In the other ninety five per cent there is no obvious reason.

At which point, something very strange happens. Instead of calling this ‘a raised blood pressure where no cause can be found,’ the medical profession decided to turn a clinical sign into a disease. This disease is Essential Hypertension, which literally means ‘a raised blood pressure where no cause can be found.’ But you have to admit that essential hypertension sounds rather more impressive.

Once it became a de-facto disease, it can be ‘treated.’ And so it came to pass that, over time, a whole series of drugs were developed. Some reduce the blood volume, some relax the blood vessels, some block the production of hormones designed to raise blood pressure, and others prevent the heart pumping too hard.

They come by names such as thiazide diuretics, beta-blockers, alpha-blockers, angiotensin converting enzyme inhibitors, angiotensinogen II inhibitors etc. etc. After statins, these are the most prescribed type of medications. Around the world, hundreds of millions of people take them each and every day.

This mass pharmacological assault happened before anyone had actually established that lowering blood pressure was actually beneficial. There had been a couple of short term studies on people with very high blood pressure. These did show benefit.

However, when it came to moderately raised blood pressure, there were absolutely no studies at all. Yes, you did read that right. No studies. It was not until the 1970s that anyone actually set out to answer this rather fundamental question by setting up a major study. The UK Medical Research Council (MRC) study.

Recruitment started in 1973. Seven hundred thousand people were contacted, and half a million people accepted an invitation to participate.  As is the way with such things, this enormous initial number was whittled down to just under eighteen thousand people who had a diastolic blood pressure between 90 – 109, and a systolic pressure below 200.

The eagerly awaited results were released in 1985. I remember the year well, as I was at a cardiovascular conference at the time. Everyone was convinced that that there would be major benefits.

And what were the results? Well, if you get down to the most important outcome of all, which is overall mortality, there were 248 deaths in the treated group and 253in the placebo group2. Or to put this another way: 248 out of 9000 died in the treatment arm died, and 253 out of 9000 died in the placebo arm:

Overall mortality: 248/9000 = 2.75% (treatment group)

Overall mortality: 253/9000 = 2.81% (placebo)

The total difference in deaths was seven. The absolute percentage difference in deaths was 0.06% over five years. There was no difference in the death rate from heart disease.

I remember thinking at the time. ‘Blimey that should throw the cat amongst the pigeons. We are going to have to re-think this area.’ How wrong could one man be? Because the result of the MRC study was that absolutely nothing changed. There was no re-think, no fundamental review, nothing.

Men occasionally stumble over the truth, but most of them pick themselves up and hurry off as if nothing ever happened.’ Sir Winston Churchill.

Actually, it is not entirely true to say that nothing happened. Within the world of anti-hypertensive therapy a subtle, but critically important, change did take place. Whilst there was no benefit on heart disease, or life expectancy, there was a small, but statistically significant, effect on stroke. One stroke delayed for around nine hundred years of treatment.

At this point, the research community started to combine stroke and heart disease under the heading ‘cardiovascular disease’. It was then reported that blood pressure treatment reduced total deaths from cardiovascular disease. Which is true. The fact that there was no impact on Coronary Heart Disease and/or overall mortality was gradually pushed into the background

Nowadays, when people report on blood pressure lowering, the discussion is almost entirely focussed on cardiovascular mortality (which basically means stroke).

In a parallel move, researchers started to move away from outcome data e.g. death from stroke and heart disease, and began to use a mathematical model (the log-linear model) to define the success of lowering blood pressure3.

Once you decide that the lower you get the blood pressure the better this is, you no longer need measure death from heart disease and stroke and suchlike. You just measure the blood pressure reduction, feed these data into the log-linear model, then you can establish the clinical benefit you must have had.

There is just one slight problem. This model doesn’t actually work in practice. Twenty years ago Ancel Keys – the man who created the diet-heart hypothesis – concluded that the linear model was useless. Twelve years ago, a group of medical statisticians re-analysed the original data which underpinned the log-linear model and they concluded the following:

‘Shockingly, we have found that the Framingham data in no way supported the current paradigm to which they gave birth. In fact…. The paradigm MUST be false4.’

They went on to make the following statement:

‘No randomised trial has ever demonstrated any reduction of risk either overall, or cardiovascular death by reducing systolic blood pressure to below 140mmHg.’

The effect of their analysis was, as you may expect, a deafening silence. This was despite the fact that these researchers had just proved that everything that everybody believed about lowering blood pressure was wrong. The log linear model rules, lowering blood pressure is beneficial.

Nine years later, another analysis appeared. The one mentioned at the start of this article. It exactly the same thing…. again:

‘A new review has found that lowering blood pressure below the “standard” target of 140/90 mm Hg is not beneficial in terms of reducing mortality or morbidity1.’ July 2009

During that twelve year period between these two studies, the thresholds for ‘treating’ blood pressure became lower and lower. For diabetics, essential hypertension has now fallen to a systolic of 115mmHg. This definition was created from combined end-point cardiovascular data, and the log-linear model. The one that has been proved ‘shockingly’ to be false. I wasn’t that shocked.

In fact, only one thing shocks me. It is fact that you cannot get anyone to change their minds in this area. A raised blood pressure is bad, and must be lowered, full stop. Whilst I would agree that a raised blood pressure is ‘bad’ in that it is associated with and increased risk of premature death. I cannot find evidence that lowering the blood pressure does any good, no matter what the level.

The simple fact is that when blood pressure is raised, it is raised for a reason. The reason is an underlying ‘disease’. And just because you cannot find it, does not mean that it doesn’t’ exist.

Lowering the blood pressure will certainly get rid of an annoyingly high measurement, but it cannot (unless by complete coincidence), have any impact on the underlying disease…… the thing causing you to die. So, unless it is startlingly high, what good can lowering blood pressure actually do?

The answer my friend, is not blowin in the wind. The answer is ‘no good at all.’

1: http://www.medscape.com/viewarticle/705670?src=mp&spon=2&uac=97302DZ

2: MRC trial of treatment of mild hypertension: principal results. Medical Research Council Working Party: BMJ 1985;291(6488):97

3: Stamler J. Blood pressure and high blood pressure, aspects of risk. Hypertension 1991; 18(Suppl I): I–95 – I – 107

4: Port S, Garfinkel A, Boyle N:  There is a non-linear relationship between mortality and blood pressure. EHJ (2000) 21 p 1635-1638