Category Archives: Dr Malcolm Kendrick

I am a GP living in Macclesfield, having graduated from Aberdeen medical school many moons ago. This blog is my best effort at providing some balance to the increasingly strident healthcare lobby that seems intent on scaring everyone about almost everything. Is there a foodstuff that is safe to eat anymore? Is there any activity that does not cause cancer or heart disease? Sausages…..get thee behind me Satan.

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

Do Low Cholesterol Levels Cause Cancer?

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We live in a world where a high cholesterol is now considered to be virtually the most terrible and dangerous thing known to man. Everything possible must be done to bring the level down, or else you are going to die of a stroke or heart attack.

The anti-cholesterol propaganda has been so successful that six million people in the UK now take statins each and every day to reduce their risk of heart disease. Something which, I strongly believe, future generations will look back on in amazement. ‘Did they not know that cholesterol is essential for human health….what on earth did they think they were doing?’

Can it really be true that a chemical compound, so important that the liver synthesises at least five times as much as you consume in food, can be disastrous to our health. All cell membranes need it, our brains need it, almost all of our hormones are made out of it, and it is used to make vitamin D in our skin. It has always seemed to me that having too little cholesterol is just as likely to be damaging as having too much – probably more so.

One area I have particular concerns about is cancer. For many years it has been noticed that people with low cholesterol levels are more likely to die of cancer. This has been a consistent finding, for many years, from studies done all around the world1-9.

The statin ‘zealots,’ as I shall call them, are well aware of the association between low cholesterol and cancer, and they have gone out of their way to dismiss the possibility that low cholesterol may cause cancer.

The primary argument they have used is known as reverse causality. This ‘reverse-causality’ hypothesis suggests that depressed LDL-cholesterol levels are the result of subclinical cancer (not the other way round). This idea has been put forward with absolutely no evidence to support it. Despite this, it has been accepted without question.

It is true that if you have advanced cancer, your cholesterol levels fall. This happens for a number of interconnected reasons, including the fact that large tumours use a lot of cholesterol to divide and grow.

However, the idea that a cancer so small, that it cannot not yet be detected, is using up so much cholesterol that it lowers the total cholesterol level throughout the body, is stretching the boundaries of possibility. I would say breaking the bounds of possibility.

The second argument put forward, which is not really an argument, is the ‘how can a low cholesterol level cause cancer anyway.’ It should always be remembered that a great deal of medical research consists of bumping into effects, without understanding how it could happen in the first place – see under penicillin. See more recently under aspirin protecting against cancer. A finding as yet, without any clearly defined mechanism of action.

In short, just because you can’t easily see a mechanism of action, does not mean that it doesn’t exist.  In fact, several possible ways that cholesterol, or to be more accurate lipoproteins, could protect against cancer have been researched in some detail10.

Anyway, as I have always known must happen, the ‘reverse causality’ hypothesis has finally been laid to rest.  A recent analysis of the longest running heart disease research project in the world (the Framingham Study) has shown that low cholesterol levels predate cancer diagnosis by many, many, years. And, to quote:

“Based on these data, it would suggest that lower cholesterol predated the development of cancer by quite a long time. Now, that doesn’t necessarily speak to [low cholesterol] causing the cancer; it could have been related to something else altogether, but it’s not supportive of the hypothesis that cancer caused the low levels of LDL cholesterol. We don’t know why it predates cancer, but it would be premature to attribute it to the cancer itself.” 11

In short, it must now be accepted that cancer doesn’t cause low cholesterol levels. Which leaves the possibility that low cholesterol levels might cause cancer. This, inevitably, leads to the next question. If low levels of cholesterol precede cancer, can statins cause cancer?

The evidence is not conclusive, and I would not claim that it was. But there have been some significant warning signs from statin studies. Just to mention three. In the CARE trial12, twelve women in the statin group had breast cancer at follow up, compared on only one in the placebo group. In the PROSPER study13 there were forty six more cases of cancer in the statin group than the placebo group.

Possibly the most worrying figures come from a Japanese study which looked at nearly fifty thousand people taking statins over six years. They found that the number of cancer deaths was more than three times higher in patients whose total cholesterol was less than 4.0mmol/l at follow-up, compared with those whose cholesterol was normal or high:

‘The patients with an exceptionally low TC (total cholesterol) concentration, the so-called ‘hyper-responders’ to simvastatin, had a higher relative risk of death from malignancy than in the other patient groups.’

The authors then went on to warn:

‘Malignancy was the most prevalent cause of death. The health of patients should be monitored closely when there is a remarkable decrease in TC (cholesterol) and LDL-C (Low Density Lipoprotein ‘bad cholesterol’) concentrations with low-dose statin.’14
This is not proof of causation, but these are warning signs. Armed with the Framingham data, I believe that the medical profession has to face up to the painful reality that low cholesterol levels could be a cause of cancer, and this needs to be properly researched. We must remember that it took Richard Peto more than thirty years to prove that smoking caused lung cancer, and no statin trial has lasted longer than six.

1. Williams RR, Sorlie PD, Feinleib M, McNamara PM, Kannel WB, Dawber TR. Cancer incidence by levels of cholesterol. JAMA 1981; 245:247–52.

2. Salmond CE, Beaglehole R, Prior IA. Are low cholesterol lvalues associated with excess mortality? BMJ 1985;290:422–4.

3. Schatzkin A, Hoover RN, Taylor PR, Ziegler RG, Carter CL,Larson DB, et al. Serum cholesterol and cancer inthe NHANES I epidemiologic followup study. NationalHealth and Nutrition Examination Survey. Lancet 1987;2:298–301.

4. To¨rnberg SA, Holm LE, Carstensen JM, Eklund GA. Cancer

incidence and cancer mortality in relation to serum cholesterol. J Natl Cancer Inst 1989; 81:1917–21.

5. Isles CG, Hole DJ, Gillis CR, Hawthorne VM, Lever AF.Plasma cholesterol, coronary heart disease, and cancer inthe Renfrew and Paisley survey. BMJ 1989; 298:920–4.

6. Kreger BE, Anderson KM, Schatzkin A, Splansky GL. Serum cholesterol level, body mass index, and the risk of coloncancer. The Framingham Study. Cancer 1992; 70:1038–43.

7. Schuit AJ, Van Dijk CE, Dekker JM, Schouten EG, Kok FJ.Inverse association between serum total cholesterol andcancer mortality in Dutch civil servants. Am J Epidemiol1993; 137:966–76.

8. Chang AK, Barrett-Connor E, Edelstein S. Low plasma cholesterol predicts an increased risk of lung cancer in elderlywomen. Prev Med 1995; 24:557–62.

9. Steenland K, Nowlin S, Palu S. Cancer incidencein the National Health and Nutrition Survey I. Follow-updata: diabetes, cholesterol, pulse and physical activity.Cancer Epidemiol Biomarkers Prev 1995; 4:807–11

10: http://qjmed.oxfordjournals.org/content/early/2011/12/08/qjmed.hcr243.full.pdf?keytype=ref&ijkey=kZGZxqVjYWEOtoc

11: http://www.theheart.org/article/1375049.do?utm_campaign=newsletter&utm_medium=email&utm_source=20120325_ACC_dimanche_2

12: Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD,Cole TG, et al. Effect of pravastatin on cardiovascular eventsin women after myocardial infarction: the cholesterol and recurrent events (CARE) trial. N Engl J Med 1996;335:1001–9

13: Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM,Cobbe SM, et al. Pravastatin in elderly individuals at risk ofvascular disease (PROSPER): a randomised controlled trial.Lancet 2002; 360:1623–30.

14: . Matsuzaki M, Kita T, Mabuchi H, Matsuzawa Y, Nakaya N,Oikawa S, et al. Japan Lipid Intervention Trial. Large scalecohort study of the relationship between serum cholesterol lconcentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia. Circ J 2002; 66:1087–95.

 

Association does not mean causation

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Of all the things you should bear in mind when looking at health stories, this is probably the single most important. Association does not mean causation. The reason why this is so important is that studies that have only found associations make up the vast bulk of scare stories in the media:

Here is a typical recent headline, which you may have seen:

Eating red meat regularly ‘dramatically increases the risk of death from heart disease’

It is true that this newspaper headline does not actually state that eating red meat causes heart disease. Not quite, but very nearly, and you could be forgiven for thinking that it does. Read it again, and you will not see the word cause anywhere. It is just very implied very strongly

However, as you get into the article itself, any distinction between association and causation fades almost to nothing:

‘Senior author Professor Frank Hu, from Harvard School of Public Health in Boston, US, said: ‘This study provides clear evidence that regular consumption of red meat, especially processed meat, contributes substantially to premature death.

‘On the other hand, choosing more healthful sources of protein in place of red meat can confer significant health benefits by reducing chronic disease morbidity (illness) and mortality.’

The study found that cutting red meat out of the diet led to significant benefits. Replacing one serving of red meat with an equivalent serving of fish reduced mortality risk by 7 per cent.’

At this point we are heading into the territory of Bill Clinton in his impeachment trial where the meaning of words it being stretched to their very limit. ‘But what is, is?’

I defy anyone to read those paragraphs and not conclude the following:

1: These researchers proved that eating red meat causes premature death

2: The researchers further proved that cutting out red meat and replacing with fish reduced mortality risk by 7 per cent.

I don’t think you could be blamed for thinking these two things. Because that appears to be exactly what was said. Or was it? Were you just being fooled by a complex conjuring trick made up of carefully chosen words designed to bewilder.

Here are the actual conclusions of the paper:

‘Red meat consumption is associated with an increased risk of total, CVD, and cancer mortality.’

Note the word associated. Where is the word cause? It isn’t there, because this study could never, ever, prove causality. Why not? Because it was an observational study (actually it was a review of two other observational studies).

In an observational study you do not do anything active. You just study that things that people do, or eat, and see if any associations emerge. When you find an association the next question you have to ask is the following. Are you looking at yellow fingers, or smoking.

It is certainly true that yellow fingers are associated with a higher rate of heart disease Does it follow that yellow fingers cause heart disease? No, of course not, what it means is that people with yellow fingers are usually people who smoke. And smoking vastly increases the risk of dying of heart disease.

In this case the distinction between the cause and the association is blatantly obvious – or at it has become so after fifty years of research made it clear Indeed, if I were now to try and claim that having yellow fingers causes heart disease, you would look at me as though I were an idiot – and I would be.

Yet, when a study finds that eating red meat is associated with a higher risk of heart disease, we seem to rush headlong into the conclusion that eating red meat consumption almost certainly causes heart disease. But red meat could well just be the equivalent of yellow fingers.

You think not? In that case you are probably thinking that red meat contains saturated fat, and saturated fat raises cholesterol levels, and raised cholesterol levels cause heart disease. If you played this little causal chain in your mind, you would most certainly not be alone in doing so.

It is something that our brains seem hard-wired to do…

‘….our brains and nervous systems constitute a belief-generating machine, an engine that produces beliefs without any particular respect for what is real or true and what is not. This belief engine selects information from the environment, shapes it, combines it with information from memory, and produces beliefs that are generally consistent with beliefs already held. This system is as capable of generating fallacious beliefs as it is of generating beliefs that are in line with truth.’ http://www.csicop.org/SI/show/belief_engine/

We cannot seem to help ourselves from linking things together to create causal chains, or beliefs, that certain things cause other things to happen. This is emotional, it is exceedingly powerful, and deconstructing such beliefs is the work of Hercules.

In this particular case, though, you would be hard pressed to use this belief as an explanation. How do I know this? I know that because the Harvard team found that those who at the most red meat actually had the lowest cholesterol levels. This table (figures taken from the paper itself) divides people into five groups/quintiles. Those in quintile 1 ate the least red meat, those in quintile 5 the most.

Total Red Meat Intake Quintile, Servings per Day

 

Quintile

 

1

2

3

4

5

% with high

cholesterol

14.8

11.1

9.7

9.0

7.9

Pan A; Sun Qi;, ScD;  Bernstein A; et al: ‘Red Meat Consumption and Mortality:Results From 2 Prospective Cohort Studies.’ Arch Intern. Med.Published online March 12, 2012.doi:10.1001/archinternmed.2011.228

The authors chose not to make any comment at all on this finding. Although you might have thought it worth a quick mention. Had they found rising cholesterol levels with increased meat consumption you can be absolutely certain they would have presented this as a clear cut causal chain. So how did eating read meat cause an increase in the rate of heart disease? Because it just did….through some mechanism unknown to medical science? The evil power of redness.

What is far more relevant is that they also found that those who ate the most red meat also smoked the most, exercised the least, ate far more calories in total, and were more likely to have diabetes. But it was the red meat that killed them from heart disease….you think? Even if red med included pork, and unprocessed red meat included hamburgers.

This study demonstrated, as if any further demonstration were required, that a whole bunch of unhealthy lifestyle factors: smoking, taking no exercise, drinking, eating fast food are all linked together. But I think we knew this already.

To preventative medicine and beyond!

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Preventative medicine has gone completely mad and it is only going to get worse. One of the most depressing articles I have read recently (and there was plenty of competition for this particular accolade) was in the Journal of Palliative medicine. It was entitled:

‘Statins in the last six months of life: A recognizable, life-limiting condition does not decrease their use.’

Statins, as you probably know, are used to reduce the risk of dying of heart disease, strokes and suchlike. Now, I am not exactly a fan of these drugs, to put it (very) mildly. But I thought that even the most fanatical ‘statinator’ might feel that if a patient is dying of terminal cancer, then there is little point in continuing with a drug designed to reduce the risk of heart disease.

Wrong. It seems that patients with terminal cancer are prescribed statins up until they draw their final breath on this Earth. What exactly are their doctors trying to prevent here? Well, at least they didn’t die of a heart attack first? Thank God for that.

I have had personal experience with this particular madness. I was visiting a lady of one hundred and one years old in a nursing home. The nursing staff asked me if I could change her statin from a tablet to a liquid form, as she was no longer able to swallow tablets. This lady was so severely demented that she could not speak, was unable to remotely recognise any of her relatives, and was lying immobile in her bed – doubly incontinent.

I felt that, in the circumstances, it was probably best just to stop the statin, especially as they are one hundred times more expensive in liquid than tablet form. So it all seemed like an expensive action in futility. For this action I was severely criticised by the nursing home, and another doctor involved in her care. I believe I was, at one point, accused of being ‘ageist.’ Well, I didn’t really know how to respond. I wondered where we drew the line with preventative medicine, and it appears we no longer draw the line, anywhere.

We carry on forever. We give drugs to the terminally ill, the extremely old and severely demented. Once started we never, ever, stop, no matter what, until the patient is dead. Perhaps at that point I should scatter statins on their ashes, just to make absolutely and completely certain that I am not missing a trick. After all, I would hate be thought of as ‘deadist’.