Monthly Archives: April 2012

Prevention is better than cure – maybe

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[Part one- of many – probably]

The last few decades have seen medicine move inexorably towards the idea that its primary function is to prevent diseases from happening in the first place. Rather than trying to cure them after they have started. Which is a nice simple thought. It also seems an inarguably good thing. So presenting any case against preventative medicine can seem wilfully contrarian, and is often met with extreme anger….’do you want people to die!’

In truth, I do not want people to die – although I would have to add that we are all going to die anyway, whatever we do, so what would be your point exactly? No, what I want is for more people to understand that prevention is not a panacea. It can do more harm than good. Indeed, in certain cases, it can cause significant damage to health and general wellbeing.

It almost goes without saying that many preventative activities are a good thing. Clean water supply, surgeons washing their hands before operations, stopping smoking, taking exercise, and suchlike. But once you have got past such obviously useful activities, the benefit to harm ratio can rapidly become far less straightforward.

I spent some time recently reading a book by Peter Gotzsche called ‘Mammography Screening, Truth Lies and Controversy’. It helped to highlight many issues about cancer screening that have disturbed me for some time.

The first, and most important, is this. Many women have cancerous cells in their breasts. Around 40% of women in their forties, on autopsy, have detectable breast cancer(s). To balance this out, most men after forty, if you took out their prostate and sliced them open, would have detectable cancer cells present as well.

Although 40% of women have potentially detectable cancers, around 4% of women die of breast cancer.

This means that, the vast majority of breast cancers do not actually do anything very much. They sit there, and they sit there and…..presumably, many of them regress (shrink) back down to nothing at all. They cause no health problems, and a large proportion of women will die with, rather than of, breast cancer.

Increasingly, however, someone calls you in for mammography, and you have your scan, and they find a small suspicious lump. In an instant you turn from a happy healthy person, into someone with cancer – the deadly killer. At which point all hell breaks loose.

Now, if that cancer happened to be one that was going to grow and kill you, then all the crushing fear and despair, and biopsies, and operations, would be a small price to pay. But if that cancer was one of the 90% that was going to sit there doing nothing for the rest of your life, then you have paid an exceedingly heavy price indeed.

In addition to this downside, in many cases, the suspicious lump was not even cancerous at all. The mammography identified a possible cancer – and it wasn’t. In screening terms this is known as the false positive. In human terms it is known as, the most terrifying thing that has ever happened to me….. and you’re telling me it was a mistake!

There are those who take an absolutist position on this and say that ‘If even one life is saved, it is all worth it.’ Perhaps, but mammography exposes a women to a radiation dose that is around five hundred times that of a simple chest x-ray. Some estimates suggest that each mammography carries a one in two thousand risk of causing cancer.

If, over a lifetime of screening, you have ten mammograms, that represents  a one in two hundred chance that a procedure designed to pick up cancer, may actually cause it. Or maybe the risk is greater than is. Is the potential to cause cancer additive, or multiplicative? I can find no-one able to answer this particular question.

Then, of course, there is the risk that the mammogram is negative. You are reassured that you do not have cancer – but you do. So when you feel a lump you think. It’s OK, I’ve had a mammogram and I am clear. But you are not. You could have been treated, but you waited too long. This is known as the false negative.

I could go on into further downsides, but I hope to have made the general issue clear. Breast cancer screening sounds wonderful, it is presented as an absolute good, but it is not. There are significant. and not uncommon. harms. Yet such is the zealotry (I hesitated to use the word zealotry, but I can’t think of a better one) of those involved in breast cancer screening that no downsides at all are ever presented.

Screening is good, breast cancer screening is perfect….or not. Here is what Professor Michael Baum has to say on the matter:

‘After a systematic review of all websites on this subject, a recent paper in the British Medical Journal concluded that women are being coerced into screening by those organisations connected to the government or the screening industry. I am neither for nor against screening, but I am a passionate champion of informed choice for women. For an informed choice women should be treated as adults and provided with balanced information, not with propaganda.’ http://www.spiked-online.com/articles/0000000CA382.htm

Preventative medicine, and screening and scanning, has almost become a religion for those involved. Only the positives are ever mentioned, and those who dare criticise are subjected to ruthless attacks. As I will be for writing this.

Prevention is better than cure?

Sometimes. Maybe.

The Joy of Coronary Arteries (The body ain’t that simple)

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‘For every complex problem there is an answer that is clear, simple, and wrong.’ H.L Mencken

Of all the things that I find most frustrating about medicine, it is the power of the simple solution. Nothing, probably, does more damage than a fixed belief in a simple idea. The history of medicine is littered with examples. ‘You have a bad headache…..well then, let us relieve it by removing a large section of your skull.’

‘You have recurrent infection of the tonsils. Well, let us remove these two glands, designed to fight infection, and your problems with infection will be solved.’

‘You had a heart attack. Well, you must rest in bed and take all the strain off your heart for six weeks, at least.’ I have calculated that this action caused the premature death of more people than died in the first and second world wars, Stalin’s pogroms, and the holocaust, added together. No, this doesn’t happen anymore.

But many things still do.

One such thing is the obsession of the medical profession with attacking coronary arteries. The arteries that supply blood to the heart. In many people these arteries develop thickenings (plaques), which can gradually narrow the artery and reduce blood supply to the heart muscle.

This can lead to angina, and suchlike. People also believe this means that a sudden blood clot forming over a narrowing can completely block the blood supply and cause a myocardial infarction (heart attack). People think this, but it is not necessarily true. Arteries without narrowings can suddenly block too – and if they do, the outcomes are usually far worse. Oh yes, the counterintuitive world of human physiology.

Anyway. If you think that a narrow coronary artery is the equivalent of having a ticking time-bomb inside your chest, you will probably want to do something about it. In 1967, someone managed to do so:

 ‘In 1967, the Argentine surgeon Dr. René Favaloro, working at the Cleveland Clinic, successfully used a vein graft to bypass an obstructed coronary vessel. Like Edmund Hillary and Tenzig Norgay, the first climbers to reach the summit of Mount Everest, or Roger Bannister, the first to run a four-minute mile, Favaloro opened a terrain deemed beyond human reach. In coronary artery vascular surgery he sundered the barrier to the seemingly impossible. Within ten years 100,000 patients were subjected to coronary bypass operations in the U.S.; by 1990s the number had quadrupled.’ Essay by Bernard Lown.

I suppose everyone has heard of the Coronary Artery Bypass Graft (CABG), pronounced cabbage by most doctors. What a wonderful idea, you use a bit of vein (sometimes a bit of artery, if you can find one) to bypass the narrowing. Huzzah!

You would think that someone would have tried to find out if it did any good, or not. But no-one really wanted to know. This operation bypassed a narrow coronary artery, increasing blood supply to the heart. This is such a simple and straightforward idea that to question it was to question common sense itself.

Which is why we ended up with four hundred thousand people being operated on each year in the USA alone. Yet no-one had ever done a study to find out if it did any good.

The someone who did try mighty hard was Bernard Lown. He is a Nobel laureate, and he also invented the defibrillator. So he was not some unqualified nut case. However, he had become very worried about ever increasing number of interventions:

‘Dealing with the growing tide of interventions, most of which I regarded as unwarranted, was morally challenging. To remain silent was complicit. To speak out was to invite confrontation with a powerful and unforgiving establishment. One pressing question was, how could we identify the subset of coronary patients that did well without surgical treatment? To determine how to proceed entangled me in a welter of contradictory views and emotions. One thing was certain, something needed to be done.’

And so he set out to try and find out if CABGs did any good. This was very tricky as he found that the moment he did an angiogram (an x-ray test for looking at coronary arteries), anyone who had a narrowing wanted a CABG straight away. At first, could not recruit a single person into his ‘control’ arm.

Eventually, though, he did manage to study this area and he found that….

‘…we recruited 144 consecutive patients with advanced coronary artery disease. These were followed for an average period of nearly five years, during which time 11 patients died, for an annual rate of 1.4 percent. We referred only 9 patients for CABG (1.3 percent annually). These results were better than the best outcomes being reported for those undergoing CABG.’

These results were better than the best outcomes being reported for those undergoing CABG. Of course, the net effect of this was that the entire world applauded. Er, no

‘Our sense of achievement was short-lived. Leading medical journals refused to publish these findings.’

Of course, as is the way of such things, the world moved on. Instead of CABG, we now have angioplasty. This is a procedure where you open up the artery from the inside using a small balloon, or inserting a wire mesh (stent).

Angioplasty is now taking over from CABG as the intervention du jour and, guess what, it is less effective than CABG – which makes it less effective than doing something that is less effective than doing nothing. Which means that every day it grows in popularity.

Ah yes, the tyranny of the simple solution continues.

I am indebted to Paul Rosch for sending me the essay from Bernard Lown on this issue.

Does treating high blood pressure do any good?

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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