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.

Sweden gets it right

I sometimes think that I should go and live in a Scandinavian country. They get so many things right about how to run healthy, equitable, societies. In addition, the people who live there seem more balanced and, well, frankly, more grown up. So it comes as no surprise to me that if a nation was to turn round and begin the process of rejecting the absolute nonsense that a high fat diet is bad for you, then it would be a country in Scandinavia.

That Scandinavian country is Sweden1.

Now, I have been aware that there has been a movement towards a high fat low carb diet (HFLC) going on in Sweden for some years. This has been led recently by the heroic Dr Annika Dahlqvist, a General Practitioner who had been advising her diabetic patients to eat a low carb high fat diet (LCHF).

She was, of course, attacked by the idiots…sorry experts:

‘In 2007, the controversy began when two dieticians pointed out to Sweden’s National Board of Health and Welfare that LCHF dietary advice recommended to diabetic patients by general practitioner Dr Annika Dahlqvist was not compatible with either scientific evidence or conventional practice. However, following a report by diabetologist Dr Christian Berne, Dahlqvist was cleared.’

Cleared of what, exactly? Advising diabetic patients not to eat sugar. The mere fact that anyone could be dragged in front of the authorities for advising this just shows had completely mad the world of dietary advice has become. How entrenched the idiotic anti-fat dogma now is. How utterly divorced from reality and science.

As I have pointed out many times on this blog, and elsewhere, carbohydrates, at least all the carbohydrates humans can digest, are converted to sugar(s) in the GI system. They must be, because all that carbohydrates consist of are different number of sugar molecules bonded together in different ways. When you break them to bits in the digestive system, they become simple sugars.

As we all know, people with diabetes have problems with high blood sugar levels. So, dum de dum….let me think. Should diabetics eat carbohydrates/sugar, or should they eat fats. Yes, you are right, they should eat fats. This is a complete no brainer.

But, of course, the argument goes that diabetics are more likely to die of cardiovascular disease and eating fat increases cholesterol levels, and this increases your risk of cardiovascular disease. Well, this could obviously be a problem if any part of that causal chain were true. But it is all nonsense. As the latest Swedish report from the SBU (Swedish Council on Health Technology Assessment) makes clear (after reviewing 13,000 studies), a low carb diet leads to the terrible dangers of

‘…a greater increase in HDL cholesterol (“the good cholesterol”) without having any adverse effects on LDL cholesterol (“the bad cholesterol”). This applies to both the moderate low-carbohydrate intake of less than 40 percent of the total energy intake, as well as to the stricter low-carbohydrate diet, where carbohydrate intake is less than 20 percent of the total energy intake. In addition, the stricter low-carbohydrate diet will lead to improved glucose levels for individuals with obesity and diabetes, and to marginally decreased levels of triglycerides.’2

In short, when they looked at all the evidence, they found that low carb/high fat diets raise HDL cholesterol (the so-called ‘good’ cholesterol). They have no effect on LDL levels; they also lower blood sugar levels and triglyceride (VLDL) levels. All good and healthy, and all of which bascially means that insulin resistance has been reduced – the underlying cause of diabetes.

In reality all that the Swedes really ‘discovered’ is the quite astonishing fact that eating a high carbohydrate diet is bad for you, and worse for you if you are a diabetic. Well, blow me down with a feather. They have found exactly what a working knowledge of human biology/physiology would tell you would happen.

But we live in a wold controlled by entrenched stupidity, dogma, and the financial interests of massive companies who are making billions selling tasteless low fat mush. These companies know that the only way you can make low fat food, e.g. low fat yoghurt, taste like anything half palatable is to stuff it with sugar. Cheap, nasty, and damaging to health – also driving the ever increasing weight gain and diabetes in the Western World.

Why is everyone in the Western World becoming obese? Because we are replacing fat with sugar in many foodstuffs. The obesity ‘epidemic’ started at exactly the same time as the idiots, sorry experts, decreed that a healthy diet was a diet full of carbs. Which was, and remains, the exact and complete opposite of the truth.

However, anyone who dares to stand up and state the truth, gets dragged in from of organisations such as the National Board of health and Welfare. Eventually, however, the truth does emerge, as it must. Because the truth never dies. It can be stomped on, squashed, concreted over and napalmed. However, it lives on, taunting those who do everything in their power to deny its existence.

The truth is that all of the dietary advice we have been bombarded with for the last forty years about the dangers of fat consumption has been utterly and completely and damagingly wrong. Of course there will be a backlash against the Swedish report – there always is. Various powerful idiots, sorry experts, will be pushed in front of cameras to make various denunciations of the Swedes and their damaging and dangerous conclusions. The strings of these idiots will be jerked in unison by faceless marketers in companies that promote low fat spreads, and the like. Yes, you know who you are.

And yes, this stuff does make me angry. It is killing people prematurely, millions of people, all around the world.

1: http://coconutoil.com/sweden-becomes-first-western-nation-to-reject-low-fat-diet-dogma-in-favor-of-low-carb-high-fat-nutrition/

2: http://www.dietdoctor.com/swedish-expert-committee-low-carb-diet-effective-weight-loss

P.S:

Question:            ‘What do you call five hundred dieticians lying at the bottom of the ocean?’
Answer:               ‘A good start.’

So much for scientific debate

I thank Ted Hutchinson for pointing me at this article in the Irish Independent. It appeared on the 5th of October, and I reprint it in full, here.

A LEADING vascular surgeon, whose research review concluded cholesterol-lowering medicines may do more harm than good for many otherwise healthy people, has been gagged by the Health Service Executive.

Sherif Sultan, a senior medic at University College Hospital, Galway, reviewed a range of studies of statins and found a lack of evidence to show they should be given as a means of prevention to healthy people with high cholesterol but no heart disease.

Mr Sultan and his surgeon colleague Niamh Hynes said lifestyle changes to reduce cholesterol were better because this allowed people to avoid the risk of statins’ side effects.

However, in a statement last night, Dr Pat Nash, a cardiologist and the group clinical director in University College Hospital said the recently published views of his colleagues were “not representative” of those in Galway or neighbouring hospitals.

“As group clinical director of the West/North West Hospitals Group, and a working cardiologist, I wish to reassure patients that statins are safe,” said Dr Nash.

“These are very important, well-validated drugs for the treatment of elevated cholesterol. We have extensive evidence to show their benefit and to show that they improve outcomes for patients with heart disease and stroke and that they have a role in preventing heart disease and stroke.

“As always, if patients have any concerns, they should not discontinue their medication without discussing with their GP or consultant.”

Asked to comment, Mr Sultan said: “I have received an official warning from the HSE and have been instructed not to liaise directly with the press in my capacity as a HSE consultant.” However, he said he could continue to comment as a consultant vascular surgeon at the Galway Clinic, where he has a private practice.

The HSE declined to comment on the reasons for ordering Mr Sultan not to speak as a public consultant. He said he stood by his analysis of the role of statins in otherwise healthy patients with high cholesterol. He pointed to another recently published review on exercise versus drug therapy in the management of pre-diabetes and cardiovascular disease.

“That ‘British Medical Journal’ analysis showed the superiority of exercise over drug therapy extends even to secondary prevention (where patients have developed disease)1.

This story has been rumbling on for a while. A report on the research paper can be found in the Irish Medical Times from a couple of weeks before.

The under-reporting of findings on major adverse effects of statin therapy and the way in which they had been withheld from the public, and even concealed, is a scientific farce, claims new Irish research.

Mr Sherif Sultan, Consultant Vascular and Endovascular Surgeon, and Niamh Hynes, Clinical Lecturer In Vascular and Endovascular Surgery, claimed their study, just published in the Journal of Endocrine and Metabolic Diseases (2013, 3, 179-185) highlights the major side-effects and dangers of statins.

They said there is a categorical lack of clinical evidence to support the use of statin therapy in primary prevention. They are both based in the Western Vascular Institute at University College Hospital Galway and the Galway Clinic. “Odds are greater than 100-to-1 that if you’re taking a statin, you don’t really need it2..

I was sent the original paper by Sherif Sultan a couple of months ago, and it is very scathing about statins….. very scathing indeed. It even suggests, perish the very thought, that pharmaceutical companies may have been trying to present statins in the best light possible. I find such a suggestion almost impossible to believe. Knowing how completely ethical these companies are.

Anyway, I suppose the key phrase in all of this sorry episode is the following:

The HSE declined to comment on the reasons for ordering Mr Sultan not to speak as a public consultant.”

If the Health Service Executive were to comment, what could they say to justify their actions?

The hell with scientific debate. He should just damned will shut up and say what we want him to say?”

“How dare anyone criticise the sainted statins which work in mysterious ways their wonders to perform.”

We expect utter loyalty from those who work in the glorious Irish Health Service. Those who do not support us can expect serious sanctions……”

On balance, declining to comment is probably the best policy for the HSE. Because if you start trying to justify why you are gagging a researcher for trying to tell the truth then, well, you will end up having to justify state censorship of scientific debate. Which never looks that good on the printed page, I find.

I feel I should sign off this blog with a quote from George Orwell, taken from 1984. “Being in a minority, even in a minority of one, did not make you mad. There was truth and there was untruth, and if you clung to the truth even against the whole world, you were not mad.”

1: http://www.independent.ie/irish-news/hse-gags-surgeon-after-cholesterol-drug-claims-29636095.html

2: http://www.imt.ie/news/latest-news/2013/09/study-claims-to-highlight-the-ugly-side-of-statins.html

Please sign – most important issue

I received this post and felt the immediate need to post it on my blog, to allow as many people as possible to sign a petition to stop pharmaceutical companies hiding adverse event data on their drug FOREVER. This is a hugely important issue for humanity.

See below…

Sorry for the Mass Posting here but we have just posted a Swedish translation of the RxISK petition calling for Access to Clinical Trial Data.

Some of you will have signed this but even if you have read on because we have a mission for you.

Two years ago, the European Ombudsman ruled that the European Medicines Agency should open up access to Clinical Trial Data for anyone who applied from anywhere in the world.

Six months ago two US pharmaceutical companies AbbVie and InterMune took a legal action against EMA that has closed down access to all trial data for all drugs for all doctors and researchers anywhere in the world…

Some of you may not have heard of AbbVie. Until recently they were Abbott Laboratories, one of the biggest pharmaceutical companies in the world.

They make Humira, a monoclonal antibody used for Rheumatoid Arthritis, Crohn’s Disease, Psoriasis and other conditions. It is the best selling drug in the world today, and projected to be the best selling drug of all time.

This is one of the most important legal actions in Healthcare ever. At a recent meeting in Bruxelles AbbVie made it clear that a main reason to keep clinical trial data confidential was to hide adverse event data, although there may be other issues like a Trade War with China.

You can read about this and see the whole video here

Essentially AbbVie are asking the Courts to grant their Corporation the privacy rights of an individual – a very powerful wealthy individual.

But the key help is this. If this legal action succeeds Adverse Event data will be hidden for ever.

So we’d love you and anyone you know to sign a petition calling on AbbVie to drop their legal action against the EMA’s policy of open access to clinical trial data. The petition is here or in Swedish as above

This petition is as much for anyone who may be prescribed drugs as for those prescribing them – so we are hoping to spread word about it generally.

In addition to signing, we are trying to get every country in the world to sign.

We have 72 of the 187 countries in the world signed up but would love to have all.  If any of you have contacts in any Eastern European, African or South East Asian countries that you could get to sign this it would be really excellent

Thanks, David

David Healy
Professor of Psychiatry, Hergest Unit,
Bangor, Wales LL57 2PW, UK

david.healy54@googlemail.com
davidhealy.org

Too much medicine – dementia

I am, in general, distinctly sceptical about mass screening programmes. Politicians, however, just love them. They use the complex scientific principle of ‘A stitch in time, save nine.’ Or else the concept of pure logical reasoning known as ‘Better to be safe than sorry.’

On a very superficial level screening is obviously a good thing. You pick up a disease early, then you ‘treat’ it, then it is gone. Huzzah! Pink ribbon anyone? Indeed, how could anyone possibly argue with such an obviously sensible thing to do? So sensible that we are drawn to this idea like moths to a flame. We flutter around it, unable to break free from its mesmerising power.

I am not suggesting that all forms of screening are useless. My favourite screening test is to take someone’s pulse. You can tell within about twenty seconds, or less, if someone has atrial fibrillation (AF). If they do, this is a condition that can be effectively managed, reducing the risk of stroke by nearly a half.

This test costs nothing, requires no great skill, is non-invasive, and…… of course it is not on any screening programme anywhere in the world (as far as I know).  Strange, as it fulfils virtually all of the criteria of a successful screening test. As outlined by the WHO as far back as 1968

World Health Organization guidelines on assessing the value of a screening test

  • The condition should be an important health problem.
  • There should be a treatment for the condition.
  • Facilities for diagnosis and treatment should be available.
  • There should be a latent stage of the disease.
  • There should be a test or examination for the condition.
  • The test should be acceptable to the population.
  • The natural history of the disease should be adequately understood.
  • There should be an agreed policy on whom to treat.
  • The total cost of finding a case should be economically balanced in relation to medical expenditure as a whole.
  • Case-finding should be a continuous process, not just a “once and for all” project

Instead, we have vastly expensive, poorly sensitive tests for diseases where our treatments are poor, and our knowledge of the natural history of the disease is virtually non-existent. I am not discussing cancer screening here as that is a far more nuanced area.

What I am talking about here, specifically, is dementia screening. Which is the latest bonkers, poorly thought though, damaging bit of stupidity that the UK Govt is now intent forcing on General Practitioners in the UK – and the US. And that was the polite version of my real views.

Here is what the BMJ has to say about dementia screening:

‘Conclusions—Current policy is rolling out untested and uncontrolled experiments in the frailest people in society without a rigorous evaluation of its benefits and harms to individuals, families, service settings, and professionals.

In fact, the entire article is a paean of common sense, and I would recommend anyone to try and get hold of it, and read it. But journals place themselves behind pay for view barriers nowadays, so you probably can’t.

However on of my favourite passages is the following

What will be the effect of encouraging more widespread and earlier diagnosis of dementia? A meta-analysis of the diagnostic accuracy of clinical tools used by general practitioners, including 15 studies on dementia, estimated that if, a clinician saw 100 consecutive community based patients with a prevalence of dementia of 6%, using current criteria he or she would correctly identify four of the six but would incorrectly identify dementia in a further 23 people.

In short, if there were six out of a hundred patients in the community with early stage dementia. The average clinical would miss two of them, and state that twenty three without the condition had it. My, how fantastically accurate.

A good screening test needs to pick up (or not miss) well over ninety five per-cent of people who have the condition, and not misdiagnose more than one – or two – in a hundred.  A misdiagnosis (false positive), is not a trivial thing. ‘I am sorry to tell you Mrs Smith, that you have dementia.’ The effects of being told this can be utterly devastating.

Finances, family planning, the sense of despair that you are going to end up unable to recognise your close family. Dribbling to yourself in a nursing home, doubly incontinent.  These are all the things that flash through people’s minds when told they have dementia.

But don’t worry, we haven’t got any effective treatment for it either….. you will be glad to know….’ The doctors shall then happily inform the three out of four people that they have MISDIAGNOSED. Whilst thirty per cent of those with dementia wander off happily, reassured that they don’t have dementia – when they have actually got it.

There are times, when I look at the direction of travel in medicine, that I almost give in to despair. There is not enough money to pay for many proven and effective treatments. We are closing hospital beds and making nurses redundant. Our psychiatric services are virtually exterminated due to lack of funding, with severely distressed people unable to access any support.

Yet we can find money – it seems- to fund a completely useless. Sorry, not completely useless. Dementia screening is far more that completely useless – it is actively damaging. We have money to pour into an actively damaging, vastly expensive screening programme to pick up a disease that we cannot actually treat in any meaningful way. Gasp…thud. Noise of head hitting desk.

Luckily, there is always malt whisky to dull the pain.

’Political drive to screen for pre-dementia:
not evidence based and ignores the harms of diagnosis.’

Deadly Medicines and Organised Crime: How big pharma has corrupted healthcare

Deadly Medicines and Organised Crime: How big pharma has corrupted healthcareA bold title for a blog indeed, but not mine (I almost hasten to add). This is the title of a new book by Professor Peter Gotzsche.  I have ordered it, and started to read it. Gotzsche does not hold back. As the introduction states:

We take so many drugs is that drug companies don’t sell drugs, they sell lies about drugs. This is what makes drugs so different from anything else in life…Virtually everything we know about drugs is what the companies have chosen to tell us and our doctors…the reason patients trust their medicine is that they extrapolate the trust they have in their doctors into the medicines they prescribe. The patients don’t realise that, although their doctors may know a lot about diseases and human physiology and psychology, they know very, very little about drugs that hasn’t been carefully concocted and dressed up by the drug industry…If you don’t think the system is out of control, then please email me and explain why drugs are the third leading cause of death…If such a hugely lethal epidemic had been caused by a new bacterium or a virus, or even one hundredth of it, we would have done everything we could to get it under control.

This is a short blog. The only reason I have written it is to make you aware that this book exists, and to urge you to buy it, and read it.

Disclosure of Interest (D.O.I). I have absolutely no financial interest in this book. I know Peter Gotzsche through e-mail conversations.

What is your blood pressure (BP)?

Central arterial blood pressure

(What is it, don’t like it. Pay attention it could save your life)

It is a pressure that is measured, almost exclusively, by placing a cuff around one arm – usually the left. The cuff is then inflated to a point whereby all blood flow is stopped. If you have placed a stethoscope over the brachial artery (artery in the arm) you will hear nothing at this point. Because there is no blood flow, and nothing to hear.

As the pressure in the cuff is lowered, a noise will be heard as the blood first starts to squeeze through. This is defined as the systolic blood pressure i.e. the point of highest arterial pressure, just after the heart contracts. A sharp tapping noise would be the best description.

As you lower the pressure in the cuff, the noise changes and muffles. Eventually, there will come a point where the blood is flowing through the brachial artery all the time …the point of ‘lowest’ blood pressure. Once this pressure is reached, the noises in the brachial artery cease. This is defined as the diastolic blood pressure. (The pressure does not reach zero, because the heart pumps once again to boost the pressure again).

All of this means that your blood pressure is presented as two figures. The highest recorded pressure (systolic) over the lowest (diastolic).

Historically, blood pressure measured in millimetres of mercury. Because, in the good old days, blood pressure meant how many millimetres of mercury could be pushed up a tube by the force of the cuff being inflated round the arm. If you used water in the tube, instead of mercury, we would measure in metres, not millimetres.

Despite the fact that mercury has nothing to do with the process any more, the measurement is still called mmHg (millimetres of mercury that can be pushed up a narrow tube). A normal blood pressure is around 120/70. If you are an Olympic weightlifter, the blood pressure can reach over 300mmHg during a lift. Which is pretty high.

In a nutshell that is what your blood pressure is…. but what does it mean? The pressure in your arm is certainly not the same as the pressure in your finger, or your brain. The pressure will be different in the right and left arms, as the blood has further to go before it reaches your right arm. It will be different if the cuff is put in a slightly different place on the arm. It will also be different if you are stressed, if the cuff is a bit small – or slightly too big.

In short, your blood pressure can be all over the place. Which is why a single measurement is not used to define high blood pressure. You need at least three. In fact, this is not nearly enough either. To diagnose someone with high blood pressure you really need to monitor the blood pressure over a twenty four hour period – using ambulatory monitoring. This helps to get rid of ‘white coat’ hypertension (high blood pressure). A phenomenon whereby the act of a healthcare professional wrapping a cuff round your arm sends your blood pressure sky high.

Because of the difficulties of measuring the blood pressure, it is estimated that around twenty five per cent of people diagnosed as having hypertension – do not actually have high blood pressure at all. Which means that they are taking drugs that they do not need. Costing the NHS at least a billion a year, and a great deal more around the world (yes, this truly is an international blog).

The other major problem with measuring the blood pressure at the arm is that it may not reflect the blood pressure just after the blood leaves the heart. The central arterial pressure. This is important, because this is the most critical pressure of all. There are a number of reasons why this is so.

Firstly, the central arterial pressure is the pressure in the aortic arch (the U bend in the aorta (biggest artery in the body)). This represents the pressure that sends blood straight up the carotid arteries and into the brain, which is clearly important with regard to stroke risk. [This where two, critically important, small BP sensing organs sit]

It is also the pressure that has the greatest impact on the kidneys. The renal arteries branch directly from the aorta itself. Therefore the central arterial pressure is closely monitored by the kidneys, which are the primary organs of blood pressure control. In addition, the central pressure has the greatest impact on the aorta itself. A relatively common cause of death is a ‘ballooning’ of the aorta (aortic aneurysm).  Such aneurysms can burst, with obviously catastrophic results.

Now, there is no doubt that the pressure at the arm is related to the central arterial pressure. It must be – to a certain degree. And for most people measuring at the arm is probably a good enough estimate of the ‘true’ blood pressure.

However, if your blood pressure measurement is high, or low, or you are on blood pressure medication….then the pressure measured in the arm becomes increasingly unreliable. It can even become misleading i.e. your pressure seems to be going down in the arm – but it is not going down as much centrally1. (It may even be going up.)

‘The results of the Conduit Artery Functional Endpoint (CAFE) study also suggest that the central aortic blood pressure may be more predictive of cardiovascular events, such as stroke and heart attack, than traditional peripheral (brachial) blood pressure measurements. CAFE was the first study to repeatedly measure central aortic pressure in a major clinical outcomes trial and the first to show that central aortic pressure is a plausible mechanism to explain the better clinical outcomes seen in patients treated with amlodipine-based therapy in ASCOT.’

Of course, central arterial blood pressure is somewhat difficult to measure. Up till fairly recently you had to insert a catheter, with a measuring device, into to the femoral artery, and push it up to the aortic arch. This would not be highly practical during a consultation with a GP. So central BP is very rarely measured. But it would be best if it could…

The anomalies of blood pressure trials

Now to introduce another thread to this discussion. Which is the fact that, if you choose to look at the clinical trials on blood pressure lowering with an objective eye, there is almost no correlation between the amount the blood pressure is lowered (at the arm) – and any clinical outcomes. By which I mean that the rate of heart attacks and strokes do not relate to the degree of blood pressure lowering.

To quote a series of bullet point in the European Journal of Cardiology entitled ‘There is a non-linear relationship between mortality and blood pressure’:

  • Drugs that lower the blood pressure by about the same amount have very different effects on outcomes
  • Cardiovascular benefits of ACE-inhibitors (Angiotensin Converting Enzyme – Inhibitors), independent of blood pressure, are not observed with calcium antagonists, despite the latter having more pronounced effects on blood pressure.
  • HOPE (Heart Outcomes Prevention Evaluation study) demonstrated that ACE inhibitors provided diverse and profound cardiovascular benefits, with only trivial differences in blood pressure between the treatment and control groups
  • ALLHAT (Antihypertensive and Lipid Lowering treatment to prevent Heart Attack Trial) showed a dramatic difference in cardiovascular risk between alpha blockers and diuretics, with essentially no difference in their effect on blood pressure. The investigators of ALLHAT concluded ‘blood pressure lowering is an inadequate surrogate marker for health benefits in hypertension.

This is extremely important, because for many years, most of the ‘evidence’ on blood pressure treatment has been based on a statistical model known as the ‘log-linear’ model. This model states that ‘the relation of blood pressure to risk of death is continuous, graded, and strong, and there is no evidence of a threshold.’ (Stamler). The model itself, and that statement, were almost entirely based on evidence from the Framingham Heart Study. The study that your doctors will use to calculate your risk of dying of heart disease.

Essentially, according the log-linear model, the lower your blood pressure (measured at your arm), the better. And the more that drugs lower it, the better. At least this is the thinking that is currently used.

However, thirty years ago Ancel Keys (yes, him) concluded that the linear model, in terms of the relationship of overall and coronary heart disease death to blood pressure was ‘unjustified’. Ten years ago, the authors of the article ‘There is a non-linear relationship between mortality and blood pressure’ further concluded (after reviewing the Framingham data – the data upon which your doctor will determine your future risk of dying of CVD)…the following:

‘Shockingly, we have found that the Framingham data in no way supported the current paradigm to which they gave birth. In fact, these data actually statistically rejected the linear model. This fact has major consequences. Statistical theory now tells us that the paradigm MUST be false ….’ (Their italics and capital letters).

In short, the blood pressure model that is used worldwide is simply, plain damned wrong. The reality is that the amount the blood pressure is lowered in the arm bears little, or no, relationship to any benefit on heart attacks and stroke.  How can this be? Well, there are two major reasons for this. One of which I am covering in this article. The other, later. Now to introduce another thread.

How do blood pressure lowering drugs work?

I am going to avoid being too technical here – which is tricky. I am also, only focussing on the four most commonly used blood pressure lowering agents/classes.

1: Diuretics. These drugs make you pass more urine, by blocking sodium re-absorption by nephrons in the kidney. This means that you pass a lot of urine (diuresis). This puts you into a state of mild dehydration, thus reducing blood volume. Exactly why this lowers your blood pressure is a moot point. (You may think you know. However, it is almost certainly far more complicated that what you are thinking – I certainly don’t understand it)

2: Beta-blockers: These, effectively, slow your heart rate and also decrease the pumping force of your heart. An unwanted effect is that they also cause peripheral blood vessel constriction.

3: Calcium channel blockers: These reduce the force of contraction of the heart, dilate blood vessels (arteries not veins), and slow the heart rate at bit. All of which lowers the blood pressure.

4: ACE-inhibitors: (a bit more explanation is required to explain how they work). The kidneys are the primary organs that control blood pressure. If they pick up that the BP is too low, they release a substance called renin. Renin triggers a whole series of other hormones into action. Ending up with increased angiotensin II levels.

This hormone has multiple effects. It reduces urine production, by increasing sodium absorption. It causes constriction of arteries, and stimulates the pituitary gland to produce anti-diuretic hormone (ADH) – thus reducing urine output.  It does several  other things too, all of which result in the blood pressure going up.

As is the complex way of the body, the kidney doesn’t actually produce angiotensinogen II  when the blood pressure drops(which would seem logical). The kidney produces renin, the liver produces angiotensinogen. When these two hormones met, angiotensinogen is converted into angiotensin I. Then angiotensin I is further converted to angiotensin II by an enzyme called Angiotensin Converting Enzyme (ACE). (There will be an exam later)

All of this means that angiotensin II is the main, active, substance. Once it has been produced, angiotensin II goes off to do all its blood pressure raising things. If, however, you give an ACE-inhibiting drug (ACE-inhibitor), angiotensin II production is blocked, and the blood pressure will fall.

Anyway, as I hope has now become clear, the blood pressure lowering classes of drugs all work though very different mechanism. They all lower the blood pressure at the arm, but what else are they doing?

Beta blockers tend to constrict peripheral blood vessels. Calcium channel blockers and ACE-inhibitors tend to dilate them. Diuretics are mainly neutral on blood vessel diameter.  ACE-inhibitors also do something else that is extremely important. They stimulate Nitric Oxide synthesis in the blood vessels themselves, which both dilates arteries, and increases blood vessel flexibility.

In short, the effect on central and peripheral blood pressure of various BP lowering medications will be very different.

Bringing these thoughts together

You may think, why now? Why is he quoting articles, and research, from many years ago? Well, you have to bear in mind that it is a long time since anyone did a placebo controlled blood pressure lowering study. It would be considered unethical to do so now (such are the alleged enormous benefits of BP lowering). So, there isn’t really any fresh information. Just the monitoring of one drug vs. another, and assuming benefit based on the degree of BP lowering – using the log-linear scale.

However, it has now become possible to measure central blood pressure by simply using a cuff placed round the arm. I have had this process explained to me many times, and cannot really understand how it is done. But the results are repeatable, and accurately reflect central blood pressure. Which is all that really matters.

When you do this, you can also measure the velocity of the pulse wave, which is an accurate indicator of arterial flexibility – and thus arterial health. If your arteries are stiff this is a worrying sign, and reflects poor arterial health. The more flexible your arteries are, the better.

At last, hoorah, instead of wrapping a simple cuff round people’s arms, we can use a complicated cuff to look at two more, really important things. The central blood pressure, and arterial flexibility. This gives us far more information.

Perhaps most importantly, we can monitor the effects that different blood pressure lowering medications have, beyond their impact on the BP measured at the arm. We can see if central pressure is increased, or decreased, or if arterial compliance (flexibility) is improved.

I think that this is a major breakthrough in medical practice. So much so, that I have acquired a machine for myself, and will be using it on a regular basis. I fear it will take the wider medical profession about twenty years or so for this to become an accepted way of measuring blood pressure. This is about the normal lead time for new ideas to become standard practice.

Sweden 1967

Sweden in 1967

It may, of course, take longer. Or never happen at all. At the risk of going off on a major tangent, I remember looking at pictures of roads Sweden in 1967. This was when they switched from driving on the left, to driving on the right. 3rd Sept 1967

As you can see from the picture, a bit of a mess. But imagine if any country tried to do it now, with the extra number of cars and lorries, and roads, and signs. This would probably be just too difficult.

How about changing the way we look at measuring blood pressure. We have always measured blood pressure using a simple cuff on the arm. All the clinical studies on BP lowering were done using this technique. All the data, all the guidelines….everything, is now based on doing BP measurement in this way.

Just imagine what happens if someone now says. Hold on, this is not good enough. The measurement is inaccurate and potentially confusing, and it doesn’t’ really tell us what we need to know. Let us start again. Let us drive on the right, not the left.

In the meantime, whilst the medical world grapples (or chooses not to grapple) with a trillion dollar problem, you can do yourself a favour and get your blood pressure measured centrally.

More on this later.

1: http://www.medscape.org/viewarticle/518570

2: Port S, et al: ‘There is a non-linear relationship between mortality and blood pressure.’ European Heart Journal (2000) 21, pp. 1635 – 1638

Beradinelli-Seip Syndrome – stick that in your pipe and smoke it

We are told, ad-nauseam, that obesity is the main cause of type II diabetes. This, allegedly, follows a very simple causal chain.

Obesity > insulin resistance > raised blood sugar levels

For those not familiar with the term Insulin resistance, this is the condition whereby various organs in the body become gradually more insensitive to insulin, which forces insulin levels higher to keep the blood sugar levels down.

Eventually the resistance to insulin becomes so great that the blood sugar levels rise anyway – despite the high insulin levels.  Alternatively, or in parallel, the pancreas gives up fighting against the resistance and insulin production becomes ‘burnt-out’. Whichever process is dominant, they both result in sugar levels become very high, and you will be diagnosed with type II diabetes.

At this point I have to state that I have always found it weird that a raised blood sugar level can be defined as a disease, when it is clearly nothing of the sort. In my world a ‘disease’ is the underlying malfunction which causes various signs and symptoms to occur (of which a raised blood sugar level would be one).

Everyone agrees that insulin resistance is the basic underlying cause of a raised blood sugar level a.k.a. type II diabetes. Despite this we define the blood sugar level itself as the disease.

‘A high blood sugar level is type II diabetes….end of.’

‘So, if we lower the sugar level, we have cured the disease?’

‘Yes. Now do shut up.’

Clearly bonkers, but let us not expect too much in the way of logic in medicine. Anyway, that is a slight distraction from the main theme here, which is the: obesity > insulin resistance > raised blood sugar levels discussion.

Now, for reasons that I am not going to fully bore you with here (but maybe at a later date), I have always had problems with this causal chain.  Primarily, that it has never made much sense to me.  Insulin resistance occurs almost exclusively in two tissues; the liver and skeletal muscle, and NOT in adipose tissue. So why would having too much adipose tissue make you insulin resistant? Answers on a post-card please*.

In order to pursue this thought further I started to look at evidence from Sumo Wrestlers. These are the most obese people on the planet. At least they are if you use BMI to define obesity. Yet, none of them have type II diabetes (at least not, whilst in training). For example:

Abnormally large waist circumferences, which were determined by the criteria established by the Japanese Society of Internal Medicine, were present in all Sumo wrestlers (100%), and fifteen Sumo wrestlers (83%) had high abdominal visceral fat areas (>100cm2). Only 2 subjects were categorized with high serum triglyceride levels, and 5 subjects were classified with low HDL-C levels by established criteria. None of the Sumo wrestlers had fasting hyperglycemia (high blood sugar levels) (0%)1

Interesting, is it not, that the most obese people on the planet do not have type II diabetes (although some of them have a degree of insulin resistance – for reasons that I may explain at a later date). Yes, I know exactly what you are now thinking. They do not have diabetes because they exercise a lot. It’s true, they do.  But does that not make it more likely that a lack of exercise is the true of cause of insulin resistance, rather than obesity….yes, of course it could certainly mean that.

In truth, finding very obese people without diabetes does not rule out obesity as the cause of diabetes. But it does rule out obesity as being both ‘necessary’ and ‘sufficient’.  At this point I need to explain the concept of necessary and/or sufficient.

It was Koch who first tried to determine a process of logic to describe whether or not something may be a true cause of a disease, or just a chance association. He introduced us to Koch’s postulates, and also the concept of necessary and/or sufficient.

For example, it is known that the bacteria vibrio cholarea causes cholera. In order to get all the signs and symptoms of cholera it is ‘necessary’ to be infected with this organism. However, infection with vibrio cholarea does not cause cholera in everyone. If you are a fit and healthy adult you can shrug off the infection with only mild symptoms. Koch proved this by drinking a glass of water known to be infected with vibrio cholarea and developing only mild symptoms of the disease

Thus it can be stated therefore that infection with vibrio cholarea is ‘necessary’ to cause cholera. However it is not, on its own, ‘sufficient.’ Other factors are needed.  On the other hand, if you could find people with cholera who had not been infected with vibrio cholarea, then you would have to declare that vibrio cholarea was neither necessary, nor sufficient, to cause cholera. So it could NOT be the cause of cholera.

This is obvious, and inarguable.

So, moving back to type II diabetes.  Can you find people with type II diabetes who are of normal weight? Or, to stretch this concept to the limit, can you find people with type II diabetes who have no adipose tissue at all? Surely not, you say. Surely impossible.

At this point I shall introduce you to ‘Berardinelli-Seip Congenital Lipodystrophy’. This condition affects about one in ten million people. So it is hardly common, but that is not the point. The point is that the primary abnormality in Berardinelli-Seip Congenital Lipodystrophy is a lack of functional adipocytes – which means that those who suffer from this condition do not have fat cells, and cannot store fat. Ergo, that they are extremely lean. The leanest of the lean, the least obese of the least obese.

From time to time I describe this condition to doctors. At which point I somewhat cheekily ask them to guess what percentage of people with Berardinelli-Seip Congenital Lipodystrophy have type II diabetes.  I say cheekily, because they inevitably get the answer wrong. They always, without exception, answer pretty much as follows:

‘Obviously, none of them.’

The correct answer is, of course, ‘Every… single…one…of…them.’ [Gasp, sounds of people collapsing to the floor in shock etc.]

Now, if you can understand why this is true, you are at least one step on the road to understanding type II diabetes. Or to be more accurate, what is the true underlying cause of insulin resistance and high blood sugar levels. You will also understand that obesity has only a small and indirect part to play in this process; that BMI has no relevance to the issue, and that the simple causal chain: Obesity > insulin resistance > raised blood sugar level……is wrong.

Of course obesity is closely associated with diabetes – to state otherwise would be nuts. However it is not the cause of type II diabetes. It is caused by it. By which I mean that obesity is (in major part) caused by that the underlying process that also leads to insulin resistance and high sugar levels. There is a causal chain here, but it is not Obesity>insulin resistance>raised blood sugar levels.

More on this later, once your brain has become unscrambled.

*Yes, for those who know about this area, you can talk about visceral fat, but this is another more interesting and completely different discussion. I am also only discussion type II diabetes, not type I (which is a completely different condition altogether).

1: http://connection.ebscohost.com/c/articles/84569721/metabolic-profiles-fat-distribution-japanese-college-sumo-wrestlers

 

811 deaths and counting

There is a doctor in the USA called Duane Graveline who I know well. He trained as an astronaut, when such things were seen as exciting. He was very much mainstream in his prescribing and thinking about medicine, until he was started on statins. He took them happily, until he suffered an episode of transient global amnesia. A complete loss of memory, re-booting his brain to the age of about eight.

On the first occasion he had no idea what had happened. He thought he could have had a stroke, but after investigations nothing was found. He asked if the statin could have caused this, and was told no – not a chance. So he started on statins again, and suffered another episode, the same as the last.

He then started investigating and found that thousands of others had suffered from episodes of transient global amnesia whilst on statins. A very, very, rare thing to happen to anyone, but increasingly common nowadays. I wonder why? Dr. Graveline then started to develop a neuromuscular disease, similar to amyotrophic lateral sclerosis (ALS) which he attributes to the statin. Statins can certainly cause neuropathy – but I shall say no more on this issue at present.

Dr. Graveline is not so keen on statins now, nor does he believe that cholesterol causes heart disease – having looked at the evidence again with a fresh eye. For those who do not know, he has a website www.spacedoc.com. Here are listed all of the many adverse effects of statins, and the suffering of many thousands of people.

He believes that the authorities are, basically, turning a blind eye to the many and varied problems with statins. So he has laboriously gone through the Food and Drug Administration (FDA) database of Adverse Drug Events (Medwatch), to find out just exactly how many deaths statins have caused.

This is extremely difficult to analyse as the coding system in Medwatch is complex, poorly linked and many things – frankly – do not seem to make sense. Whilst going through this stuff is an absolute nightmare, it can be done – although you have to make some assumptions along the way.

What Dr. Graveline did was to look for case of rhabdomyolysis (catastrophic breakdown of muscle tissue) linked to statins. Rhabdomyolysis is a pretty specific, and well-accepted, adverse effect of al statins. However, it is considered as so vanishingly rare as to be not worth bothering about by most doctors.

Rhabdomyolysis carries a very high mortality rate, because the waste products of dissolving muscles travel to the kidneys, where they block up the nephrons, causing acute kidney failure. In around ten per-cent of cases rhabdomyolysis is fatal. So you can assume, with reasonable accuracy, that for every ten reported cases of rhabomyolysis, you will get one death. You will also get a number of people with destroyed kidneys who end up on dialysis – hey ho.

At this point I should also point out that adverse drug events are widely known to be a massively under-reported. It is difficult to be certain on the exact figures. However, having read many papers on this subject the general feeling is that about 1 – 5% of all events are actually reported by anyone – ever. Which means that any figures in Medwatch can be pretty reliably multiplied by twenty to one hundred? Which is a topic for another day.

Anyway, with this pre-amble out of the way, I have copied Dr. Graveline’s blog on statins (with his full permission). What he has found is that, over a six year period there were 8,111 cases of rhabodmyolysis reported to Medwatch associated with statins. This represents, at least, 811 deaths in this period. [If you were to multiply this figure by twenty, this is 16,200. Multiply by one hundred and you have 81,110.]

A few years ago one of the statins called Baycol was rapidly removed by the FDA after sixty people died from rhabdomyolysis whilst taking statins. Well, all statins can cause rhabdomyolysis. Hundreds have died, probably more, since Baycol was yanked from the market. Yet there is absolute radio silence on this issue.

Below is Dr. Graveline’s blog…

Relative risk of Statin Associated Rhabdomyolysis

A recent study comparing the relative risks of muscle problems with the use of the various statin drugs has recently been reported. Generally the risk of muscle adverse effects varies with the strength of the statin used except for the statin fluvastatin (Lescol). Lescol, usually considered to be the weakest of the commonly used statins now shares with rosuvastatin (Crestor), the strongest of the statins, in being consistently linked to higher adverse muscle events relative to the other commonly used statins. Atorvastatin (Lipitor) and simvastatin (Zocor) showed intermediate risks and pravastatin (Pravachol) and lovastatin (Mevacor) had the lowest risk rates. Designating rosuvastatin’s and fluvastatin’s relative risk as 100%, comparative rates for atorvastatin, simvastatin, pravastatin, and lovastatin were, respectively, 55%, 26%, 17%, and 7.5%.

     There were a total of 186,796 case reports listed within the Adverse Event database (Medwatch) during the study period 1 Jul 2005 to 31 Mar 2011. Choosing rhabdomyolysis as one of the more discrete and credible of the muscle diagnoses, a total of 8,111 cases of rhabdomyolysis were reported during this study period, averaging 1,350 cases yearly. Sidney Wolfe MD has previously estimated the statin associated rhabdomyolysis death rate to be 10 percent (giving a total of 811 deaths during this 6 year 4 month time period). Of the total number of rhabdomyolysis cases, fluvastatin was involved in 164, rosuvastatin in 1146, simvastatin in 3395, atorvastatin in 1641, pravastatin in 267 and lovastatin in 161.

     Returning to the death rate estimate of 811, this strikes me as extraordinarily high and I cannot believe I am just now discovering this. Back in the Baycol crisis of 2004, sixty deaths caused FDA to rise up and Bayer to take its problematic product off the shelves. Six years later, 811 deaths do not even deserve a mention. What has happened? Where is the media uproar that we had back in 2004? I knew the Medwatch figures for Lipitor because I had obtained a copy of the Medwatch data and counted the rhabdomyolysis cases myself. I counted 2731 cases of rhabdomyolysis from the period 1997 to 2011 from Lipitor alone which fits quite well with this recently published work. So I had a heads up. I predicted the total rhabdomyolysis cases would be 6,000 for all the statins never suspecting I would underestimate by several thousand.

     Medwatch exists for FDA to monitor these outrageous post marketing events and report back to the medical community. Where is the FDA report? This is incredible!

The most unutterable balls

A couple of night’s ago, I was watching a programme called ‘Long Live Britain’ on the BBC, co-presented by Phil Hammond. He is a UK doctor whom I greatly admire, and who mostly talks common sense. So I hesitate to criticise him. But on this programme I heard him say these very words to a volunteer on the programme (sic) ‘A lifetime of eating fatty food has made your liver fatty……’  In truth, he may have used slightly different words, but I cannot bear to watch again.

He then went on to present a lengthy clip of a very unwell lady with (I presume, though not stated), non-alcoholic steatohepatitis NASH. This is the name for a damaged, fatty, liver. A condition that can worsen and worsen and may, eventually, lead to liver failure.

Sorry Phil, but when I heard you say that eating fat caused a fatty liver, I had to switch the television off and take a few deep breaths, lest my blood pressure became too high.

What is it about diet that no-one has even the faintest damned idea what they are talking about, especially when I comes to fat consumption. I think we have demonised fat for so long that you can say anything about fat and, so long as it is sufficiently damning; no-one dares question anything you say. Science goes straight out the window.

A.N. Idiot:                           ‘Did you know that eating fat can make your liver explode.’

A.N. Other Idiot:                ‘OMG, I never knew that.’

A.N. Idiot:                           ‘It’s true. It must be, I saw it on the telly.’

Well, here are a few facts that really are facts. When you eat fat it is absorbed in the small bowel, turned into triglycerides, and packaged into a lipoprotein called a chylomicron. Chylomicrons are then fed directly into the bloodstream via the thoracic duct – bypassing the liver completely.  As they pass fat cells, the cells strip almost all of the fat out of them, so the chylomicrons shrink down and down in size, becoming chylomicron remnants. Once almost all fat is gone, these remnants are absorbed into the liver.

As should be clear from this, at no point in this process does the vast, vast, majority of fat we eat get anywhere near the liver. It is carried from the bowel directly into adipose tissue.  So, Phil, how does eating fat make your liver fatty…exactly? When the liver has no part of play in the absorption, transport and storage of any fat we eat? Oh, sorry, you’re right, it can’t.

Carbohydrates, on the other hand, now here you are talking. All the carbohydrates we eat are converted into glucose and/or fructose in the gut [apart from fibre, and starch, which we cannot digest]. Glucose and fructose then pass directly into the liver where, if your body’s sugar stores are full, they are converted into…you guessed it…fat. [Your body can only store about fifteen hundred calories of energy as glucose/sugar before the stores are full – which is not a lot].

Imagine, if you will, a body with full sugar stores* – this would be most people, most of the time. You eat carbohydrate a.k.a. proto-sugar. With sugar stores full, there is nowhere for this excess sugar to go, so the liver converts it all into fat a.k.a. triglycerides. The liver tries to stick this excess triglyceride into a lipoprotein called a VLDL (Very Low Density Lipoprotein). However, this process is complex, so the liver starts to fill up with fat.

At the same time insulin does battle with the liver, in order to drive lipogenesis (the making of fat from sugar) in the liver. Which means that you are more likely to end up with diabetes. This is not rocket science. This is basic human metabolism/physiology. And you know what, the way to reverse this process is…TO EAT FAT.

The simple fact is that there is no way on God’s earth that eating fat can give you a fatty liver. However, the process by which eating excess carbohydrate could give you a fatty liver, and then diabetes, is simple and straightforward. Yet we have a BBC programme, with a real doctor on it, stating the exact opposite.

I suppose I don’t really blame Phil Hammond too much. We have all been fed with such unutterable balls about the dangers of eating fat for so long now that the science behind nutrition long since became an inconvenience. ‘Do not bother me with facts, for my mind is made up.’

Or ‘don’t bother me with the fats; I am going to kill myself eating carbohydrates.’ Long Live Britain indeed.

*sugar/glucose is stored in the body as glycogen, a polymer of glucose (lots and lots of glucose molecules stuck together). The body does this to reduce the amount of water required to encircle individual glucose molecules.

Who shall guard the guardians?

(Quis custodiet ipsos custodes?)

Mainstream medicine increasingly relies on Guidelines. Well, they are called guidelines, but increasingly they carry the force of law. In many countries if you try to practice outside the wise and infallible guidelines you may lose your license to practice medicine. In the US, you may well be dragged into court, and if you have not been following the guidelines, you will be sued. You can even be gaoled (or jailed, as we say in the UK).

In short, guidelines are very serious and important things indeed, and they now rule medicine with a rod of steel. In the UK up to 50% of general practice time is spend ensuring that all patients are constantly monitored to ensure that various guidelines are rigorously followed. Is the BP low enough, the cholesterol low enough, have you checked blood sugar levels etc.

But where do guidelines come from – exactly? Who gives people the right to sit on guideline committees? What are the entrance requirements? Who shall guard the guideliners?

The answer is, perhaps shockingly, that there are almost no rules to this. If a group, such as the National Institutes for Health in the US, decides to set up a committee to decide on, for example, what is the healthy level for cholesterol lowering, what happens? They ask a number of Key Opinion Leaders to join the committee. In this case the NCEP (National Cholesterol Education Programme – which is a committee, not a programme).

In 2004 this committee decided that cholesterol levels should be lowered far more aggressively than in the past. Based on, as far as I could see, very flimsy evidence.  Could it be that that committee was, in some way, biased in favour of cholesterol lowering companies?  A number of people, including me, demanded to see if any of the eight invited members of this hugely important committee had financial conflicts.

With much reluctance, the conflicts were revealed (I have highlighted, in bold, the companies who marketed cholesterol lowering agents at the time.) See below

ATP III Update 2004:  Financial Disclosure of NCEP members

Dr. Cleeman: (Chairman) has no financial relationships to disclose.

Dr. Grundy: has received honoraria from Merck, Pfizer, Sankyo, Bayer, Merck/Schering-Plough, Kos, Abbott, Bristol-Myers Squibb, and AstraZeneca; he has received research grants from Merck, Abbott, and Glaxo Smith Kline.

Dr. Bairey Merz: has received lecture honoraria from Pfizer, Merck, and Kos; she has served as a consultant for Pfizer, Bayer, and EHC (Merck); she has received unrestricted institutional grants for Continuing Medical Education from Pfizer, Procter & Gamble, Novartis, Wyeth, AstraZeneca, and Bristol-Myers Squibb Medical Imaging; she has received a research grant from Merck; she has stock in Boston Scientific, IVAX, Eli Lilly, Medtronic, Johnson & Johnson, SCIPIE Insurance, ATS Medical, and Biosite.

Dr. Brewer: has received honoraria from AstraZeneca, Pfizer, Lipid Sciences, Merck, Merck/Schering-Plough, Fournier, Tularik, Esperion, and Novartis; he has served as a consultant for AstraZeneca, Pfizer, Lipid Sciences, Merck, Merck/Schering-Plough, Fournier, Tularik, Sankyo, and Novartis.

Dr. Clark: has received honoraria for educational presentations from Abbott, AstraZeneca, Bristol-Myers Squibb, Merck, and Pfizer; he has received grant/research support from Abbott, AstraZeneca, Bristol-Myers Squibb, Merck, and Pfizer.

Dr. Hunninghake: has received honoraria for consulting and speakers bureau from AstraZeneca, Merck, Merck/Schering-Plough, and Pfizer, and for consulting from Kos; he has received research grants from AstraZeneca, Bristol-Myers Squibb, Kos, Merck, Merck/Schering-Plough, Novartis, and Pfizer.

Dr. Pasternak: has served as a speaker for Pfizer, Merck, Merck/Schering-Plough, Takeda, Kos, BMS-Sanofi, and Novartis; he has served as a consultant for Merck, Merck/Schering-Plough, Sanofi, Pfizer Health Solutions, Johnson & Johnson-Merck, and AstraZeneca.

Dr. Smith: has received institutional research support from Merck; he has stock in Medtronic and Johnson & Johnson.

Dr. Stone: has received honoraria for educational lectures from Abbott, AstraZeneca, Bristol-Myers Squibb, Kos, Merck, Merck/Schering-Plough, Novartis, Pfizer, Reliant, and Sankyo; he has served as a consultant for Abbott, Merck, Merck/Schering-Plough, Pfizer, and Reliant.

http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3upd04_disclose.htm

Of course, as people have stated to me, the mere fact that there were seventy two financial conflicts of interest does not mean that the guidelines themselves were biased. But you know what, I don’t believe it. Imagine if eight Supreme Court judges, ruling on any issue, had seventy two direct financial conflicts of interest to do with that issue…..Well, the outcry would never end.

Yet doctors, it seems, are beyond any suspicion – of any sort. There is not the slightest possibility that any doctor would ever do anything wrong….We are, after all, superior beings. ‘But, what’s that you say skippy…. hold on.’

‘Despite a 2-year-old scandal discrediting key evidence, current guidelines relying on this evidence have not been revised. As a result of physicians following these guidelines, some researchers say, it is possible that thousands of patients may have died each year in the UK alone. It is unlikely that a true understanding of the damage will ever be known…..

The guidelines, which were published in 2009, were based on analyses of the available trials. The strongest evidence came from the DECREASE family of trials, which appeared to strongly support perioperative beta-blockade, and one other large trial, POISE, which raised concerns that beta-blockers might lead to an increase in deaths

In 2011, however, faith in the reliability of the DECREASE trials was shattered as a result of a scientific misconduct scandal centering on the principal investigator of the studies, the now disgraced Dutch researcher Don Poldermans. The issue was further complicated because, in addition to his key role in the trials, Poldermans was the chairman of the committee that drafted the guidelines.’ http://cardiobrief.org/2013/07/31/european-heart-guidelines-based-on-disgraced-research-may-have-caused-thousands-of-deaths/

Oh well, maybe not.

The fact is that, wherever you look, guidelines are being developed by doctors who have widespread conflicts of interest. And if you go a step further back to review the studies that the guidelines are based on, they are run by, and written up by, doctors who have enormous conflicts of interest. Although sometimes, these conflicts are just…well, forgotten about.

For example, a few opinion leader were ‘named and shamed’ by the Journal of the American Medical Association, when someone pointed out that a number of the authors of the original paper they wrote might just have slipped up in declaring their conflicts:

Unreported Financial Disclosures in: ‘Association of LDL Cholesterol, Non–HDL Cholesterol, and Apolipoprotein B Levels With Risk of Cardiovascular Events Among Patients Treated With Statins: A Meta-analysis.’

….the following disclosures should have been reported: “Dr Mora reports receipt of travel accommodations/meeting expenses from Pfizer; Dr Durrington reports provision of consulting services to Hoffman-La Roche, delivering lectures or serving on the speakers bureau for Pfizer, and receipt of royalties from Hodder Arnold Health Press; Dr Hitman reports receipt of lecture fees and travel expenses from Pfizer, provision of consulting services on advisory panels to GlaxoSmithKline, Merck Sharp & Dohme, Eli Lilly, and Novo Nordisk, receipt of a grant from Eli Lilly, and delivering lectures or serving on the speakers bureau for GlaxoSmithKline, Takeda, and Merck Sharp & Dohme; Dr Welch reports receipt of a grant, consulting fees, travel support, payment for writing or manuscript review, and provision of writing assistance, medicines, equipment, or administrative support from Pfizer, and provision of consultancy services to Edwards, MAP, and NuPathe; Dr Demicco reports having stock/stock options with Pfizer; Dr Clearfield reports provision of consulting services on advisory committees to Merck Sharp & Dohme and AstraZeneca; Dr Tonkin reports provision of consulting services to Pfizer, delivering lectures or serving on the speakers bureau for Novartis and Roche, and having stock/stock options with CSL and Sonic Health Care; and Dr Ridker reports board membership with Merck Sharp & Dohme and receipt of a grant or pending grant to his institution from Amgen. http://jama.ama-assn.org/content/307/16/1694.3.full?etoc

Not a bad little list. As you can see, Dr Ridker had board membership with Merck Sharp and Dohme…… a company that has made billions from selling statins. Now, here is he is authoring a paper on the benefit of statins (which will be used to develop guidelines on cholesterol lowering), and he simply forgot about this conflict of interest. As for the others, well, they’re also busy people; things must have just slipped their minds, such as thirty three separate financial conflicts.

For this terrible crime against the integrity of medical science, none of them can ever again do medical research, or author a medical paper, or sit on guideline committees. Cue, mad cackling laughter. As you may expect, absolutely nothing happened at all, apart from the publication of that statement you in the Journal in the American Medical Journal (JAMA).

I am sorry, but the system of developing guidelines is, frankly, bust. It has been for many years, but it is a very big and dangerous looking nettle to grasp, and no-one, currently has the will to do it.

Someone, somewhere, needs to ensure that guidelines, and the evidence they are based on, and the interpretation of that evidence, is of the highest quality – and free from potential bias, and financial conflicts of interest. We are about as far from this happy state of affairs as I am from being invited onto any guideline committee, ever, anywhere.

And that, my friend, is a very, very long way away indeed. You would need to Hubble telescope to see across distances as vast as that.

 

Proving that black is white

Last week I was going through some old files, and presentations, in a vague effort to clean up my computer. Whilst looking a one of many thousands of studies I had filed away I came across this paper: ‘Clarifying the direct relation between total cholesterol levels and death from coronary heart disease in older persons1.’

I read it, and immediately recalled why I kept it. For it came to the following, final, conclusion:

 ‘Elevated total cholesterol level is a risk factor for death from coronary heart disease in older adults.’

I remember when I first read this paper a few years ago. My initial thought was to doubt that it could be true. Most of the evidence I had seen strongly suggested that, in the elderly, a high cholesterol level was actually protective against Coronary Heart Disease (CHD).

However, when a bunch of investigators state unequivocally that elevated cholesterol is a risk factor for heart disease, I try to give them the benefit of the doubt. So I read the damned thing. Always a potentially dangerous waste of precious brainpower.

Now, I am not going to dissect all the data in detail here, but one sentence that jumped out of the paper was the following:

‘Persons (Over 65) with the lowest total cholesterol levels ≤4.15 mmol/L had the highest rate of death from coronary heart disease, whereas those with elevated total cholesterol levels ≥ or = 6.20 mmol/L seemed to have a lower risk for death from coronary heart disease. ‘

Now, I can hardly blame you if you struggled to fit those two quotes together. On one hand, the conclusion of the paper was that .. ‘Elevated total cholesterol level is a risk factor for death from coronary heart disease in older adults.’ On the other hand, the authors reported that those with the lowest total cholesterol levels had the highest rate of CHD; whilst those with the highest cholesterol levels had the lowest rate of CHD.

Taken at face value, this paper seems to be contradicting itself…. utterly. However, the key word here, as you may have already noted, is seemed. As in… those with elevated total cholesterol levels ≥ or = 6.20 mmol/L seemed to have a lower risk for death from coronary heart disease. ‘

Now you may think that this is a strange word to use in a scientific paper. Surely those with elevated total cholesterol levels either did, or did not, have a lower risk of death from CHD? Dying is not really something you can fake, and once a cause of death has been recorded it cannot be changed at a later date. So how can someone seem to die of something – yet not die of it?

The answer is that you take the bare statistics, then you stretch them and bend them until you get the answer you want. Firstly, you adjust your figures for established risk factors for coronary heart disease – which may be justified (or may not be). Then you adjust for markers of poor health – which most certainly is not justified – as you have no idea if you are looking at cause, effect, or association.

Then, when this doesn’t provide the answer you want, you exclude a whole bunch of deaths, for reasons that are complete nonsense. I quote:

‘After adjustment for established risk factors for coronary heart disease and markers of poor health and exclusion of 44 deaths from coronary heart disease that occurred within the first year, (my bold text) elevated total cholesterol levels predicted increased risk for death from coronary heart disease, and the risk for death from coronary heart disease decreased as cholesterol levels decreased.’

Why did they exclude 44 deaths within the first year?  Well, they decided that having a low cholesterol levels was a marker for poor health, and so it was the poor health that killed them within the first year.

The reason why they believed they could do this is that, a number of years ago, a man called Iribarren decreed that the raised mortality always seen in those with low cholesterol levels is because people with low cholesterol have underlying diseases. And it is these underlying diseases that kill them. (What, even dying from CHD. And how, exactly does CHD cause a low cholesterol levels….one might ask).

In truth, there has never been a scrap of evidence to support Iribarren’s made-up ad-hoc hypothesis. [A bottle of champagne for anyone who can find any evidence]. However, it is now so widely believed to be true, that no-one questions it.

Anyway, without chasing down too many completely made-up ad-hoc hypotheses, the bottom line is that this paper stands a perfect example of how you can take a result you don’t like and turn it through one hundred and eighty degrees. At which point you have a conclusion that you do like.

Young researcher: (Bright and innocent)  ‘Look, this is really interesting, elderly people with low cholesterol levels are at greater risk of dying of heart disease.’

Professor: (Smoothly threatening) ‘I think you will find…. if you were to look more carefully, that this is not what you actually found….. Is it? By the way, how is your latest grant application going?’

Young researcher: (Flushing red at realising his blunder) ‘Yes, by golly, how silly of me. I think I really found that elderly people with high cholesterol levels are at a greater risk of dying of heart disease.’

Professor: ‘Yes, excellent. Be a good lad, find a good statistician to make sure the figures make sense, and write it up.’

For those who wonder at my almost absolute cynicism with regard to the current state of Evidence Based Medicine, I offer this paper as a further example of the way that facts are beaten into submission until they fit with current medical scientific dogma.

As a final sign off I would advise that any paper that has the word ‘clarifying’ in its title, should be treated with the utmost suspicion. I think George Orwell would know exactly what the word clarifying means in this context. Facts do not need clarification.

 

1: Corti MC et al: Clarifying the direct relation between total cholesterol levels and death from coronary heart disease in older persons. Ann Intern Med. 1997 May 15;126(10):753-60

You are a very black swan indeed

Here is Wikipedia on the wisdom of Karl Popper:

“The classical view of the philosophy of science is that it is the goal of science to prove hypotheses like “All swans are white” or to induce them from observational data. Popper argued that this would require the inference of a general rule from a number of individual cases, which is inadmissible in deductive logic. However, if one finds one single black swan, deductive logic admits the conclusion that the statement that all swans are white is false. Falsificationism thus strives for questioning, for falsification, of hypotheses instead of proving them.”

Sorry, although I am a great fan of Popper, his language is a bit, well, pedantic.  What he is saying here is that science starts with a hypothesis e.g. ‘all swans are white.’ If you find white swan after white swan, then you will mildly strengthen the hypothesis. However, once you find one black swan, the hypothesis is dead.  (Unless you decree that, as all swans are white, a black swan cannot – by definition – be a swan).

One of the great white swans of cardiology is that Familial Hypercholesterolaemia (FH) causes heart disease. When I give talks to other doctors informing them that the cholesterol hypothesis is bunk, one of the ‘facts’ that is triumphantly used to knock me down is that ‘People with Familial Hypercholesterolaemia die very young from heart disease.’ Case proven, raised cholesterol causes heart disease, now move on.

A little bit of context is needed here. Familial Hypercholesterolaemia (FH) affects about one in five hundred people. It is a genetic condition where those who have it (I refuse to use the words suffer from it) have very high Low Density Lipoprotein (LDL) levels. As everyone knows LDL is known as ‘bad’ cholesterol, which is considered to be the number one risk factor for heart disease. (Of course LDL is not cholesterol at all but, hey, why let scientific accuracy get in the way of…. Well, science).

Goldstein and Brown established that the cause of FH is a lack of LDL receptors on cells. LDL receptors are the things that bind on to LDL molecules and then remove them from the bloodstream. Cells manufacture LDL receptors when they are low on cholesterol and need more.

Once the receptor is made it is pushed out through the cell membrane to attract an LDL molecule. When an LDL molecule has been caught, by binding on to the receptor, the LDL and the attached receptor are pulled back into the cell and broken down. Because they function this way, LDL receptors only work once. If a cell wants more cholesterol, then it needs to manufacture more LDL receptors.

Clearly, if there are not enough LDL receptors being manufactured, the entry of LDL into cells is restricted. This means that blood levels of LDL rise, and you will be diagnosed with Familial Hypercholesterolemia. If, that is, you have a blood test.

Moving sideways for a moment I need to mention that most people with FH are heterozygotic, by which I mean they carry one gene for FH. Their LDL levels are therefore about double that of the surrounding population. However, those with homozygotic FH (carrying both genes) have LDL levels that can be twenty times ‘normal’.  More on this group in a later blog.

Back to FH. If you have a heart attack when young, by which I mean under about 55, and you have FH, doctors will nod sagely and that that ‘it was the FH that did it.’ (If you don’t have FH, they will say it was something else that did it).

Sometimes the relatives of those dying young of CHD with FH, are contacted. It is often found that there is a higher rate of FH and premature CHD in relatives. This type of evidence has been used as proof that FH causes CHD. Maybe. Maybe not. If someone dies young from CHD, and has FH, and other relatives have a higher rate of both FH and CHD, what have we actually proved? We have proved nothing – for certain.

All we have done is to establish that relatives of people with FH and premature CHD also have FH (as they must, as it is a dominant gene) and also have a higher rate of CHD. Now, it could be that the FH is the reason for their CHD. Or it might not. It could be that something else, genetic of behavioural, is causing their high rate of CHD.

Given this problem of inherent bias, how could you tell if the FH is causing the CHD or not? Or, better, how could you falsify the hypothesis that FH causes CHD? Can you find a black swan?

Well the best way to find a black swan in this ara is to turn your study inside out. Instead of looking at people with FH and premature CHD, then looking at their relatives to find FH and CHD, you need look for premature CHD first (knowing nothing of FH status), then see if FH is more prevalent in first degree relatives.

How do you do this? Well, firstly you ask hundreds thousands of students if their father had a heart attack, or died of heart attack before the age of 55. Then you measure the LDL level of those students to see if they have FH. At the same time you find age and sex matched control students to see if they have FH.

Now, if FH really were a major cause of premature CHD you would expect to find that FH was far, far, more prevalent amongst those students whose fathers suffered CHD before the age of 55.

Such a study was done once, in the Netherlands. The results were as follows:

In the EARS (European Atherosclerosis Research Society) studies, University students whose fathers had proven CHD before the age of 55 years, were recruited …Age and sex-matched controls were recruited from the same populations for each case.

  • 2 of 1089 students with family history of CHD had FH
  • 4 of 1727 controls had FH

Thus, the prevalence of FH in both groups was not significantly different at approximately 1 in 500, which is the estimated prevalence of the condition in the general population. The evidence that heterozygote FH is, of itself, a cause of atherosclerosis is unsatisfactory.

http://www.bmj.com/content/322/7293/1019/reply

In short, when someone finally did a study on the association between premature CHD and FH, where selection bias was removed, they found that FH was no more common in those with, and without, a strong family history of CHD. This was the blackest of black swans.

However, there is a twist to this tale. Which is that this study was never published anywhere. The only reason that I know about it, is that I was reading the responses section in the British Medical Journal, and the lead investigator of the study wrote the above letter in reply to a discussion on FH. (Something more than easily missed).

I contacted him, and asked why the study had not been published. He did not provide any answer that made any sense to me. The end result of the lack of publication is that the blackest of black swans is not actually black. It is invisible. Until now, of course.

P.S. As for homozygotic FH, I shall deal with this later.

Bias, bias everywhere

For hundreds of years, medicine was driven by anecdote and personal beliefs, without the slightest supportive evidence. In the nineteen twenties the most common operation done was ‘removal of toxic colon.’ Toxic colons were believed to be responsible for almost any symptom you could think of.

  • Headache…..toxic colon
  • Anxiety…toxic colon
  • Stomach pain…toxic colon… obviously
  • Cramps…toxic colon, etc. etc.

Surgeons became blindingly wealthy cutting out significant lengths of the large bowel in those who could afford it. This operation, and the greed and stupidity that drove it, is outlined in the book ‘Doctors Dilemmas’, by George Bernard Shaw.  He went on to say that: ‘If you pay people to cut things out of you, then that it exactly what they are going to do.’

Not many people have their toxic colons removed nowadays, in fact no-one does, as the condition no longer even exists. But many people still have coronary artery bypass grafts done. Although there is not the slightest evidence that this does any good either. For more on this read Bernard Lown’s essay

Anyway, over time doctors began to recognise that if you were going to cut things out of people, or prescribe drugs, it would be nice to know if any of this activity actually did any good. And so began the dawning of the age of evidence based medicine (EBM). (Evidence based medicine is a far more recent movement than you might think, not really getting under way until the 1980s).

The individuals who really drove this forward e.g. Sackett, Cochrane, Muir-Gray were extremely hard working idealists. They were highly ethical and had the patient’s interest at heart. They taught EBM on wards with students, and looked for evidence wherever they could find it.

This was a much more difficult thing to do before the advent of the world wide web. I remember searching around for papers in medical libraries, taking literally hours to find the papers I was looking for. Something I can now do in seconds on the Internet.

In theory, of course, EBM should be a very good thing, and in some ways it has been. However, EBM relies entirely on the belief that the evidence you are using is accurate, or true, or believable, or unbiased, or whatever form of words you are most comfortable with. This may have been true once upon a time, but things have most certainly changed.

In the early days a great deal of research was carried out in major teaching Universities. Doctors and researchers would set up the trials, run them, and analyse the results. However, the turn of the millennium less than a third of drug related studies were being done in academic units.

To quote from the New York Times:

The removal of research from academic centres also gives pharmaceutical companies greater control over the design of studies, analysis of data, and publication of results.

The end result: among even the highest quality clinical research the odds are 5.3 times greater that commercially funded studies will support their sponsor’s products than non-commercially funded studies. The authors conclude, “Readers should carefully evaluate whether conclusions in randomized trials are supported by data.” Careful readers with enough time can sometimes spot discrepancies between data and conclusions in published studies. However, the drug companies typically retain control over the data from their sponsored trials so the majority of the researchers don’t have open access to the results from their own studies.’ Petersen M. ‘Madison Ave. has growing role in the business of drug research.’ New York Times, November, 2002.

In a similar, if less emotive vein, the most downloaded paper within recent medical scientific literature was written by John Lonnadis. It was entitled ‘Why most published research findings are false.’

The vast majority of people have never heard of this paper. The vast majority of those who have heard of it have never read it, and the vast majority of those who have read it, have clearly not understood the implications of what they have just read. Or, if they have…they are too frightened to do anything about it.

The shortest summary of his research is, as follows:

Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias.’ J Lonnadis.

These words sound relatively mild, but the implications are explosive. Basically, many researchers are claiming that they have proved something to be true, but all they have actually done is to manipulate their research in order to confirm what they already ‘knew’ to be true.

In essence, medical research has become horribly biased, to the point where David Sackett (a hero of mine) has virtually withdrawn from the arena

According to the founder of Evidence Based Medicine experts are hindering the healthy advancement of science.

Writing in this week’s British Medical Journal (BMJ), Canadian-based researcher, David Sackett, said that he would “never again lecture, write, or referee anything to do with evidence based clinical practice”. Sackett is not doing this because he has ceased to believe in evidence based clinical practice but, as the BMJ comments, because he is worried about the power of experts in stifling new ideas and wants the retirement of experts to be made compulsory.

Sackett claims that the prestige of experts (including himself) gives their opinions far greater persuasive power than they deserve on scientific grounds alone.”Whether through deference, fear, or respect, others tend not to challenge them, and progress towards the truth is impaired in the presence of an expert,” he writes.

He also argues that expert bias against new ideas operates during the review of grant applications and manuscripts. “Reviewers face the unavoidable temptation to accept or reject new evidence and ideas, not on the basis of scientific merit, but on the extent to which they agree or disagree with the public positions taken by experts on these matters.” http://www.abc.net.au/science/news/health/HealthRepublish_124166.htm

When the man who virtually invented evidence based medicine states that research has become institutionally biased, where can we look? I am not sure. I will leave you with a thought from Professor Bruce Charlton

The decline of honesty in science

Anyone who has been a scientist for more than 20 years will realize that there has been a progressive decline in the honesty of communications between scientists, between scientists and their institutions, and between scientists and their institutions and the outside world.

Yet real science must be an arena where truth is the rule; or else the activity simply stops being science and becomes something else: Zombie science. Zombie science is a science that is dead, but is artificially kept moving by a continual infusion of funding. From a distance Zombie science look like the real thing, the surface features of a science are in place – white coats, laboratories, computer programming, PhDs, papers, conference, prizes, etc. But the Zombie is not interested in the pursuit of truth – its citations are externally-controlled and directed at non-scientific goals, and inside the Zombie everything is rotten…..

Scientists are usually too careful and clever to risk telling outright lies, but instead they push the envelope of exaggeration, selectivity and distortion as far as possible. And tolerance for this kind of untruthfulness has greatly increased over recent years. So it is now routine for scientists deliberately to ‘hype’ the significance of their status and performance and ‘spin’ the importance of their research.

Bruce Charlton: Professor of Theoretical Medicine

So, what can be done?

Salt intake – What of Nuns?

Excess salt intake is one of the great issues in preventative medicine. Last year I watched a bus go by, with an advert for reducing salt plastered all over the side. Some restaurants have taken salt cellars off their tables, to protect customers. Many foodstuffs now have their salt content clearly labelled, with high salt content given a red sticker.

Given all of this you would think, would you not, that the case for excess salt consumption causing cardiovascular disease had been made beyond even the slightest possibility of doubt. One of the arguments in support of the dangers of salt consumption (the one that I am looking at in this article), comes from the native peoples living in the Amazon

The Amazon is an extremely low salt environment, and the average salt consumption of those living there is at very low. Several studies have found that the tribes people living in the Amazon have very low blood pressure which does not increase with age. They also have very little in the way heart disease and strokes.

Primitive societies who ingest little or no salt have no hypertension1

Proof, the anti-salt lobby cry, that it is excess salt intake that causes our blood pressure to rise dangerously.

Or is it? When presented with ‘proof’ like this I tend to look for contradiction, rather than confirmation. Are there, I wondered, other populations that fail to demonstrate a rise in blood pressure with age, that do not have a low salt consumption. My attention was drawn to nuns, living in Italy.

‘The powerful effect of psychosocial and acculturating influences on population blood pressure trends seems to be confirmed, through longitudinal observations, in the nuns in a secluded order. After initial observations had been made on culture, body form, blood pressure, diet, and other variables in 144 nuns and 138 lay women, included as a control group, a 30-year follow-up study was undertaken. Most striking were opposite trends noted between the two groups in blood pressure trend. During the follow-up period, blood pressure remained remarkably stable among the nuns. None showed an increase in diastolic blood pressure over 90 mm Hg.’

So, nuns do not develop high blood pressure as they age. What happened to the control women in this study?

‘By contrast, the control women showed the expected increase in blood pressure with age. This resulted in a gradually greater difference (delta>30/15 mm Hg) in systolic and diastolic blood pressure between the two groups, which was statistically significant.’

No difference in diet or salt consumption, yet one population developed the ‘normal’ Western rate of hypertension whilst the other did not. What did the authors of this thirty yearlong study think was the reason for this finding?

‘In conclusion, it seems reasonable to attribute much of the difference in blood pressure and cardiovascular events, to the different burden in psychosocial factor and to the preserved peaceful lifestyle of the nuns2.’

Now I do not know for sure if those living in the Brazilian rain forests have managed to preserve a traditional peaceful lifestyle – but it seems a reasonable assumption to make.

However, the main point I am trying to make here is that you do not need a low salt diet in order to prevent hypertension. You can find populations with a normal salt diet who do not develop hypertension either.

What factor, or factors, appears to link these two populations? The factor appears to be living a preserved peaceful lifestyle. This would suggest that stress is the cause of hypertension and cardiovascular disease, and not salt. Whilst association cannot prove causation, a lack of association disproves it.

1: Freis ED. The role of salt in hypertension. Blood Pressure 1992; 1: 196-200.

2: Timio M, et al: ‘Blood pressure in nuns in a secluded order: A 30-year follow-up.’ Miner Electrolyte Metab. 1999 Jan-Apr;25(1-2):73-9

What does cause heart disease?

(Part one of an occasional series)

So what does cause heart disease then, if it is not cholesterol?  This is question I am often asked – with varying degrees of accusation – by other doctors. Usually after I’ve given a talk dismissing raised cholesterol as a risk factor.

The simplest answer is that the most important causal factor of cardiovascular disease aka the development of plaques (thickenings) in the arteries, is stress (sorry about that rather clumsy form of words). However, as with many simple answers, explaining how stress causes ‘heart disease’ is a bit more complicated.

Which means, gentle reader, that we must go back to the beginning of the whole story, and weave a number of interconnected strands together.

The first strand here is to explain what ‘stress’ may be. I must admit that this is not easy, because few people have an agreed definition of stress. Many concepts are bandied about, and everyone has their own ideas on the subject, but most of them are rather too vague to be of any real use.

I define stress as a measurable dysfunction in the Hypothalamic-Pituitary-Adrenal axis (HPA-axis). But that may be jumping ahead rather too fast, and it requires many steps to get to this point. The first step is to attempt to break stress down into its component parts.

To do this, we have to start by accepting that stress has two basic components. There is the Stressor – the thing causing stress, and the Stressee – the individual affected by the stressor. Without making this important distinction, we will constantly mix up two concepts that need to be kept separate.

For example, many people talk about having a stressful day. I would immediately ask. Does this mean you were impacted on by lots of different stressors e.g. a traffic jam, a tight work deadline, your children getting ill. Or that you found yourself unable to cope with stressors that you would normally be able to cope with. Or both. [To be truthful I would rarely ask this, as I don’t want people shuffling away from me at the dinner table. But I might think it].

By looking at stress as having a cause, or causes, (the stressor), and then looking at their impact upon an individual (the stressee) we can start to disentangle the things that cause stress, from their actual impact.

In addition to this important distinction, there is also a need to accept that different stressors can create positive or negative effects, depending on how the person reacts to them.  Without getting too tangled in this issue, I will attempt put these first ideas into their simplest possible form

Stress has four distinct components:

  • Stressor – positive
  • Stressor – negative
  • Stressee reaction – positive
  • Stressee reaction –negative

Positive stressors could be:

  • Exercise
  • Winning the lottery
  • Giving a well-accepted speech
  • Watching your children perform on stage

Negative stressors could be:

  • Using cocaine
  • A close relative dying
  • Severe criticism at work/being bullied
  • Getting hit by a bus
  • Watching your army comrades being blown to bits by an IED

Some negative stressors are very short acting and, as such, the human psyche and physiology can cope and restore homeostasis (unless the trauma is gigantic). The problems start to arise when negative stressors act hour after hour, day after day, week after week. For example, being repeatedly physically or sexually abused as a child. Or being bullied day after day at work.

Problems created by a constant battering of negative stressors are also made significantly worse if your coping mechanisms are poor. Being bullied at work is not so bad if you have a good social life, a supportive partner, and a loving family. It also helps significantly if you are physically, fit and free from significant chronic disease.

If, however, you have no friends, no supportive family, and you have a chronic illness that weakens you, it does not take too much else to tip your system over the edge.

Unfortunately, early life trauma, and abuse, can leave people with very poor coping mechanisms. In addition, people who have suffered repeated negative stressors through their childhood often find themselves in a cycle of repeating negative behaviour. They are also likely to have poor coping skills, and difficulty with interpersonal relationships.

Effectively, therefore, the same ‘stressor’ can have very different effects on people, depending on their resilience. This resilience can be both psychologically and physically determined, and is hugely important. A ‘strong’ person can cope with stressors that might seriously damage a ‘weak’ person.

Some people say that stress can be simplified into the flight or fight response being constantly activated and eventually ‘burning’ out. Whilst it is true that a constantly stimulated flight or fight response is key to understanding the physiological damage that ‘stress’ causes, it is not the only factor in play.

A lack of social support is not the same thing as the flight or fight response. However, it can create significant problems with production of stress hormones. Depression is not the flight of fight response going wrong. Not having human contact, or touch, can damage your hormonal and autonomic/unconscious nervous systems just as much as being bullied.

In short, stress is not just determined by external factors, such as perceived – or real – threat. A vastly important aspect of stress lies within the individual, their responses to life events, and their resilience. As social animals, loneliness is just as damaging, if not more so, than someone threatening to fire you.

In my world, therefore, being depressed is a form of ‘stress’, and it causes exactly the same type of physiological damage as, say, post-traumatic  stress disorder. This is why you cannot look at an event in someone’s life e.g.  losing their job, or getting divorced, or suffering a car crash and loss of a limb, and score this from one to ten on how stressful this is.

  • Loss of job =2
  • Moving house = 3
  • Getting divorced = 4

For some people losing a job may be a blessed relief. For other a terrible humiliating shame. Others may just shrug their shoulders and move on.

For some of us, an apparently trivial event can be devastating e.g. a passing comment on our appearance.  Others will just laugh it off. Some years ago I was told by a doctor that stress couldn’t be a cause of heart disease because he had seen a well-off lady living in rose covered cottage in the country who had just had a heart attack.

I just replied ‘How do you know she wasn’t stressed?’ The externally idyllic existence may, in reality, be a battleground. Perhaps her smiling, smart, well-off, magistrate husband got home and beat the living daylights out of her every weekend. If so, it wouldn’t be the first time – and most certainly would not be the last.

In short, there is no point in guessing if someone is stressed. Often, there is no point asking them either. Most of us play complex internal games with regard to stress. Where it is considered a badge of honour to be ‘stressed’ and working incredibly hard – people will tell you how stressed they are. – even if they are not. Equally, if you have had a terrible upbringing, you may be so desensitised to stress that you cannot even recognise that you are suffering.

At this point I should probably attempt to bring together what makes up the concept of ‘stress’

Stress consists of stressors, and the stressee. Stressors can be positive, or negative. They can be psychological, or physical.

The same stressor can have a completely different impact on the stressee depending on their resilience.

Resilience can be damaged by such factors as:

  • Abuse in childhood
  • Long-term illness
  • A lock of supportive relationships, friends, family, church

Resilience will be improved by

  • A loving upbringing
  • Good health
  • Supportive relationships
  • Good interpersonal skills

There is no point in guessing is someone is suffering the physiological consequences of stress. Equally, there is no point in asking someone if they are stressed – they may well not know. The only way to know if someone is actually suffering from the consequences of repeated negative stressors is to measure their biochemistry and physiology.

Part two: How to measure if a person is ‘stressed’.

A simple Question – that opens a can of worms

A day or so ago I received this e-mail from a doctor in London.

Dear Dr Kendrick,

I work as a GP in Wandsworth London and I read that you don’t
believe that much in cholesterol and CHD.

I do agree up to 50% of MI patients have normal cholesterol
but some say what’s normal for UK is actually high. Is this argument valid?

Best wishes

Define ‘normal.’ Does normal mean average? If we took the average height of everyone in the UK we would find (very nearly) that 50% of those dying of CHD (coronary heart disease) were above average height and 50% below. So average is clearly normal, but then again so is being tall, or short.

However, if we decided that average height of everyone living in the UK was above ‘normal’, and we then lowered the definition of ‘normal height’ by three inches, we would find that the vast majority of people dying of CHD were now above average height. At which point we could decree that being taller than normal was a risk factor for CHD.

This would obviously be a completely bonkers thing to do. Yet, you can do it with cholesterol levels and everyone nods in general agreement.

Aha, but the argument goes that our lives are completely different than the lives of our ancestors, which has caused our cholesterol levels to be unnaturally high.

An article in the Journal of the American College of Cardiology best summed up this line of thinking. Under the heading ‘Why average is not normal’, O’Keefe, the lead author, made the claim that: ‘Atherosclerosis is endemic in our population, in part because the average LDL (“bad” cholesterol) level is approximately twice the normal physiologic level.’ In short, according to O’Keefe, our cholesterol level should be about 2.5mmol/l, not 5.2mmol/l.

He based his argument, in part on looking at the cholesterol levels of various animals e.g. elephants, and boars, and suchlike. He also used the argument that very young babies (neonates) have cholesterol level of about 2.5mmol/l. Now, in my opinion, anyone proposing this argument should have their medication increased. We should base our cholesterol levels on those found in other animals species….yes, of course we should. You mean those animal species with an average life expectancy of ten years, for example.

However, this argument is now pretty widely accepted by the medical community. We are all, everyone, living in the West, living in such an ‘unhealthy’ way that our cholesterol levels are unnaturally high. The true normal cholesterol levels is 2.5mmol/l.

Fine, if we re-set normal at 2.5mmol/l we will find that 99% of people dying of heart disease do have a ‘high ‘cholesterol level. Problem sorted, average is no longer normal, and the hypothesis that a high cholesterol level is a risk factor for heart disease is now true.

Hold on, I’ve got an idea…

How medicine now works – or doesn’t.

It may surprise some of you that read this blog that, amongst other things, I still work as a doctor in the jolly old NHS. Yes, one can be a critic and still remain inside the system….although for how long, who knows. In fact, in some ways I am quite establishment, as I sit on the main BMA negotiation committee for GPs, the General Practitioners Committee (GPC). I am also on the Local medial committee (LMC) and local negotiation committee (LNC).

From within the NHS you can more clearly see how the world of medicine is gradually going completely bonkers.

In one of my jobs I do Out of Hours (OOH) General Practice work. That is working in the evenings and weekends. In East Cheshire, where I work, we had a system which was highly rated by patients and everyone who came into contact with it. However, in line with the rest of the country we were told we were now to be incorporated into the Government’s latest and currently stupidest idea, called NHS111. The 111 bit being the single telephone number for people to call for urgent – not 999 care.

NHS111 call handlers get about six weeks training, and are supposed to act as front line troops to direct patients to the correct urgent service. Before this we had nurse triage, with experience nurses dealing with local residents and their health issue. We now have non-medically trained staff given superficial advice on how to go through a treatment algorithm. First question:  ‘Are you alive or dead?’ Not quite, but nearly.

At the end of asking ten thousand questions, or so, the call handler reaches the end of the algorithm where it states ‘You must see a GP.’ Actually, not quite true.  If there is anything actually wrong,  then the call handler tells them to phone an ambulance immediately [Yes, ambulance calls under NHS11 have risen stratospherically]. In my opinion, these people are not doing triage, they are just appointment Clerks.

As we repeatedly warned the Government NHS111 rapidly went wrong.  In East Cheshire and many other areas, NHS111 immediately collapsed the moment it went live, and we had to take back all the call handling. Why, primarily because the private providers running the service had so badly underestimated demand that the system went into melt-down, and patients were left waiting for hours to be called back. (Oh the joys of competitive tendering. In order to get the contract you have to bid so low that you cannot actually provide the service).

Anyway, we still get some calls coming through from NHS111 (A system now running in parallel – at double cost – with the old system).  With the old system we used to get the key facts e.g. a rash, non-blanching, child floppy, temp 39oC, mother worried. Now we get the following (this is an actual transcript of a very, very  simple case, with any patient identifiable data taken out – by me).

  • Symptoms: Cough
  • Case Summary
  • Disposition: The individual needs to contact the GP practice or other local service within 6 hours. If the practice is not open within this period they need to contact the out of hours service. Dx06
  • Selected care service: OOH – GP OOH Service (xxxx Base)
  • Pathways Assessment: Birth had not occurred within the last hour. An injury or health problem was the reason for the contact. The individual was breathing and conscious at the time of the assessment. Heavy bleeding had not occurred in the previous 30 minutes.
  • An illness or health problem was the main problem.
  • The individual was not fighting for breath.
  • A probable allergic reaction, a fit within the previous 12 hours or successful resuscitation were not the main reason for the assessment.
  • The child was not limp, floppy and/or unresponsive.
  • The skin on the torso felt normal, warm or hot.
  • Pathway selected – Cough
  • The individual had not coughed or vomited blood.
  • There was normal breathing between bouts of coughing.
  • Severe illness and a rash suggestive of septicaemia were not described.
  • There was no difficulty rousing.
  • There had been no episode of choking within the previous 24 hours.
  • There had been no inhalation of a hot or poisonous substance in the previous 24 hours.
  • There was no fever at the time of assessment or within the previous 12 hours.
  • There had been no previous diagnosis of heart disease, asthma or other lung disease.
  • There was not a problem for which medical advice must always be sought.
  • There were no severe coughing bouts with whooping, a red or blue face or vomiting after coughing.
  • The cough for had persisted for less than 3 weeks.
  • Instructions given were: The individual needs to be seen
  • by the GP practice or other local service within 6 hours.
  • If the practice is not open within this period they need to be seen by the out of hours service.
  • Directory of Services referral: OOH – GP OOH Service (xxxxxxx Base)
  • Advice given: Worsening
  • Advice given: If the condition gets worse, changes or if you have any other concerns, call us back.

As you can see, if you bothered to read it, 99% of this is just meaningless guff, stating irrelevant negative findings. But it does take a considerable amount of time to read. Some of it just made me despair. For example, the report states that: ‘An injury or health problem was the reason for the contact.’ Well really, how completely amazing. Someone calls a health line and they may have an injury or health problem.  Who’d a thunk?

This is followed later by…’ An illness or health problem was the main problem.’ Well at least they had narrowed it down from an injury or health problem to an illness or health problem. [So it now seems that illnesses are not health problem?]

What did I actually need to know? I needed to know that a child had a cough that was getting worse. Whilst it is possible to establish this from reading the report (just)  other key information was conspicuous by its absence. Past history of asthma, for instance (which this child had) or other respiratory problems? Any medications?  That type of thing.

As with most new initiatives in the health service I am now getting swamped with information – but the vast majority of it is completely and utterly useless, and just gets in the way of finding out what I want to know.

This, by the way, was a very small part of the report that the GP (in hours), will receive. They will get about ten more pages of other extraneous guff that they have to wade through. At some point my consultation (the only bit they are interested in) will appear so they will know what I found and what I did – and if they need to do anything. This will not be at the front of the report, no, it will be stuck in the middle, surrounded by information about when the call came in, how long it took to respond, what pathways were used etc. etc. etc. thud.

This, ladies and gentlemen, is the type of nightmare bureaucrat driven nonsense that is turning healthcare in the UK from something local, flexible, and responsive to patient needs, into a flabby form filling, algorithm following, arse-covering exercise. Millions of hours spent producing lengthy reports that have no value; they simply get in the way of providing useful information and de-skill, demotivate and de-professionalise everyone involved.

I imagine the UK is not alone in this. Somehow or another we need to fight back.

How Risky Is A Risk?

 

[I was contemplating risk the other day, when someone forwarded me an article I wrote a couple of years ago on risk. I think it is still highly relevant to what is happening today with the mangling of medical statistics]

I have only just recovered from the idea that everyone in the whole world over the age of fifty-five should spend the rest of their lives on six different medications, all stuck together in one great big pill. The following was headline from a study in the BMJ.

‘Polypill—A Statin plus 3 Blood Pressure Drugs plus Folic Acid plus Aspirin. Authors claim Polypill would reduce risk of dying from coronary heart disease by 80%. The authors of the polypill article in the BMJ made the claim that taking their polypill would reduce the risk of dying of coronary heart disease (CHD) by 80%.’

You may have seen the non-story about the, yet to be marketed polypill, peddled in the British Medical Journal (BMJ). I was stimulated to look again at the concept of risk.

Whether or not you believe their figures—and I don’t—I sense that this figure of 80% would be taken by most people to mean that eighty out of one hundred people would be saved from death if they took this magic tablet. But this figure, if true, could only possibly be a relative risk reduction. And a relative risk reduction means almost nothing, by itself.

However, because everyone’s eyes glaze over whenever you start talking about statistics, most researchers manage to get away with using relative risk reduction figures when, in reality, they should be shot for doing so. Now, here’s a challenge. The challenge to make a short article about statistics interesting. Okay, that’s not possible. But maybe a little bit interesting?

You must know the time period, and the absolute risk, for the relative risk to have any meaning

When you talk about a risk, you need to know the absolute risk of a thing happening. For example, the risk of getting struck by lightning. I don’t actually know what this risk is, but I would imagine it is about one in five million. But again, that figure means little unless you put a time scale on it. Is this a one in five million risk over a hundred years, or one year, or a day? If you don’t put a time scale in, you can claim pretty much anything you like.

For example an astronomer could attempt to shock you by stating that ‘The Earth will be hit by a big Asteroid. This is one hundred per-cent certain.’ – stunning announcement from A.N. Astronomer. Read all about it.  And of course, this is true. The Earth will be hit by a big Asteroid, sometime in the next three billion years or so. The odds ratio for this event is 1 = 100% certain. I am even willing to take a bet on it. What you probably want to know is however, is, what is the likelihood of this happening in my lifetime. Sorry, no idea.

Anyway, I hope this makes it clear that you must define risk in two ways, the possibility of the nasty thing happening, and the time period during which it is likely that the thing will happen. With lightening strikes, I would guess this is about a one in five million risk, over a five year period. Not high.

However, whilst the time factor is important, people don’t just bend statistics by ignoring the time factor. What also happens is that people inflate the risk by using relative instead of absolute risks.

For example, the chances of dying of lung cancer, for a non-smoker, are about 0.1% (lifetime risk). If, however, you live with a heavy smoker, your chances will increase to about 0.15%. (These figures are for illustration only, and are not completely accurate).

Now, you can report this in two ways. You can state that passive smoking can increase the risk of lung cancer by 0.05% – one in two thousand. Or, you can state that passive smoking increases the risk of lung cancer by fifty per cent (0.15% vs 0.1%). Both figures are correct. One is increase in absolute risk, the second the increase in relative risk.

If you are an anti-smoking zealot, then I would imagine you would prefer to highlight the second figure. The relative risk figure. And when it comes to reducing cardiovascular risk, exactly the same procedure is used (in reverse).

Let’s say that the chance of dying of CHD over the next five years, in a healthy fifty-five year-old, is 1%. By reducing this risk to 0.2%, you can claim to have reduced the relative risk of dying of CHD by 80%. The absolute risk reduction is 0.8%. Mangling statistics is easy when you know how. It’s even fun.

Anyway, now you know the difference between a relative risk and an absolute risk, and I hope this makes it easier for you to hack your way through the misinformation that spews forth from the great medical research machine.

By the way, I believe the Polypill will achieve a 0.00% absolute and relative risk reduction. But we shall see.

 

 

The Untainted Mind

 

A few weeks ago, a sixth year student at Westminster School sent me an essay she had written on cholesterol, and why it does not cause CHD. She wants to go to medical school. No one made her do any of this. She just looked at the evidence and made her mind up.  She wrote me this e-mail

Dear Dr Kendrick,

I am a final year student at Westminster School who intends to study medicine. I am extremely interested in your research and reading your book enthused my and led me to spend a large portion of my time researching studies which you and other authors on the same topic have referenced.  The Chief Medical officer came to speak to us today and after her talk I quizzed her about what I have read in your book as well as a large wealth of research I have done myself. (Attached, if you care to look, is a copy of an essay I wrote which won the top prize in school essay competition based on this research). She was extremely defensive of the cholesterol causes heart disease hypothesis and claimed that NICE had on a population level declared this to be the case. She said that the evidence did not add up on a small study level, but when studies were put together (I assume by NICE) that the conclusion is in favour of cholesterol causing CHD.

I would love to know your thoughts on this and where I can find this population based evidence.

Kind regards,

Francesca Greenstreet

I wrote back to her, to say that there was no population based evidence. Or, if there was, it very clearly demonstrated no link between cholesterol levels and heart disease. The Chief Medical Officer was just blustering – as most people do when confronted with someone who dares to question medical dogma.

I thought her essay was extremely well written and makes all the points that I have been making for years. It is just gratifying to see that the evidence on cholesterol and heart disease is clear to anyone with a brain.


In Defence of Cholesterol

The  American government, the British government and the NHS, three venerable bodies respected as sources of dietary advice, currently recommend a diet low in saturated fat and cholesterol.[1] The predominant  reason this advice is given is the accepted belief held within the scientific community that high serum cholesterol levels are linked causally with the accumulation and build up of atheromas which lead to atherosclerosis and Coronary Heart Disease (CHD).

The commonly accepted and taught theory which links cholesterol to heart disease, the Lipid Hypothesis, states that cholesterol is carried from the liver to the rest of the body’s cells in Low Density Lipoproteins (LDLs) and carried back from the rest of the body’s cells to the liver in High Density Lipoproteins (HDLs). After being transported back to the liver by HDLs, Cholesterol is broken down by the liver or passes out of the body as a waste product. The Lipid Hypothesis states that eating saturated fat raises LDL levels. The cholesterol from LDLs forms fatty deposits, atheromas, which build up beneath the endothelium of the arteries. The build up of atheromas narrows the arteries and pieces of the atheromas can break off and become lodged in narrower arteries .Clots can form in the narrowed arteries which prevent blood flow and can starve organs of oxygen and nutrients. When clots or blockages form in the coronary arteries, necrosis occurs. This leaves part of the heart muscle not contracting and relaxing and can lead to a myocardial infarction.[2]

Figure 1: Sudan-stained aorta of a rabbit fed 61 egg yolks over a 70-day period, showing lesions in red.

Figure 1: Sudan-stained aorta of a rabbit fed 61 egg yolks over a 70-day period, showing lesions in red.

The Lipid Hypothesis was brought to attention following a series of studies, the first of which was carried out by Anitschkow, a Russian scientist, in 1913. Anitschkow fed rabbits a diet of purified cholesterol dissolved in sunflower oil and examined the cells and the arteries of the rabbits after killing them. [3] Rabbits which were fed the purified cholesterol were found to have vascular lesions which bore a close resemblance to atheromas found in humans (Figure 1). Following Anitschkow’s study, Dr John Gofman led a team to similar findings and hypothesized that serum cholesterol was the cause of the lesions developing.[4] The similarity of the lesions to those found in humans suffering from CHD was catalytic in the formation of theories that a high cholesterol diet might be linked to CHD in humans.

The ideas behind the Lipid Hypothesis were formalised by Ancel Keys when, in a study in 1953, he used data from six countries to show a direct link between the percentage calories from fat in the average diet and the number of CHD deaths per 1000.[5] Furthermore, he found the incidence of CHD deaths in those six countries was best predicted by the intake of saturated fat.[6]

However, not all scientists and physicians are in agreement with the Lipid Hypothesis. Regarding Anitschkow’s rabbit study, it has been pointed out that cholesterol does not form part of the natural diet of a rabbit and thus it is possible that the rabbits had an allergic reaction to the high cholesterol diet, or that they were otherwise incapable of processing the chemical. It is significant to note that similar experiments carried out on dogs and rats showed that a rise in blood cholesterol did not lead to a rise in atherosclerosis.[7] This is potentially due to the fact that dogs and rats, unlike rabbits, consume cholesterol as part of their natural diet. The lack of cholesterol in a rabbit’s natural diet, combined with the failure to replicate the findings in dogs or rats, whose natural diets are much more similar to our own, is a significant flaw in the reasoning behind Anitschkow and Gofman’s conclusion: that a high cholesterol diet is linked to atherosclerosis in humans.

Figure 2: Keys’ (1953) selection to show relationship of fat intake to heart disease deaths of 55–59 yr. old men in 1951–53 (open circles left)and the 15 other available countries (closed circles). The relation of heart diseases to animal protein intake is on the right (Mann, 1993). (Adapted from WHO Ann. Epid. and Vital Statistics).

Figure 2: Keys’ (1953) selection to show relationship of fat intake to heart disease deaths of 55–59 yr. old men in 1951–53 (open circles left)and the 15 other available countries (closed circles). The relation of heart diseases to animal protein intake is on the right (Mann, 1993). (Adapted from WHO Ann. Epid. and Vital Statistics).

Another flaw in the Lipid Hypothesis is that Ancel Keys selected with purpose the countries for which he presented data in his study in 1953, rather than choosing them at random. “Yerushalmy and Hilleboe (1957) observed that Keys would have had available data from 22 countries, which would have given a much weaker correlation “(Figure 2).[8]

Figure 2 shows a very weak correlation between deaths per 1000 (from CHD) and percentage of calories from fat when all 22 countries are plotted on the same graph. It is interesting to note that the correlation between deaths per 1000 (from CHD) and percentage of calories from animal protein has a similar and even slightly stronger  correlation than between deaths per 1000 (from CHD) and percentage of calories from fat.  All of this data would have been available to Keys, so his focus on the link between percentage of calories from fat and the number of deaths per 1000 (from CHD) is curious.

The data sample presented by Keys gives a correlation of coefficient of +0.84, a strong positive correlation, whereas “in the simulation study by Wood (1981) on the consumption statistics of 21 countries a total of 116280 different samples of six countries were found, and the correlation between consumption of animal fat and CHD mortality varied from -0.9 to +0.9, the average being    -0.04.”[9] Such a difference in correlation coefficients between similar studies indicates some bias in Keys’ selection of the six countries or insufficient data, since Wood’s study uses many more countries and therefore is more likely to be accurate. As it is obvious that Keys had sufficient access to data from the 22 countries, it seems that his selection was biased.

There have also been many studies which investigate serum cholesterol level in relation to atherosclerosis and CHD in Humans rather than in animals. A notable example is the study led by Paterson  entitled: “Serum Cholesterol Levels in Human Atherosclerosis”. 800 patients who were permenantly confined to hospitals and 100 war veterans who were in hospital for dimiciliary care were given 2500-3000 calories a day in their daily diet, of which 25 to 35% was derived from fat. Serum cholesterol was determined annually or semi-annually and when any patients died, the severity of atherosclerosis was determined using six differnet criteria: crude morphological grading, measurement of the thickness of the largest plaque, determinations of the total lipid content, lipid concentration, total calcium content and calcium concentration. Figure 3 shows a graph showing the abscence of a correlation between Serum Cholesterol in mg.% and Total Lipid in Mg. This shows that for the criterium of total lipid content, there is no correlation in the age group of 60-69 years.

Figure 3: Total coronary artery lipid and serum cholesterol levels in patients 60-69 years. The open circles represent cases without complications of coronary atherosclerosis; the closed circles, cases with complications.

Figure 3: Total coronary artery lipid and serum cholesterol levels in patients 60-69 years. The open circles represent cases without complications of coronary atherosclerosis; the closed circles, cases with complications.

Similar findings were observed in the other age groups with a significant number of participants (70-79 and 80-89). The study concludes: “In the 58 cases in the age group 60-69 years, significant relationships between the serum cholesterol and the severity of the disease were found only once in 40 statistical analyses, and the complications of atherosclerosis were just as frequent in cases with low serum cholesterol levels (150-199 mg. %) as in cases with moderately high ones (250-299 mg. %).”[10]Considering the emphasis from the government and the NHS to reduce cholesterol and saturated fat intake because cholesterol causes heart attacks, this seems to be a remarkably weak correlation.

The Paterson study was not alone in its findings: Sigurd Nitter-Hauge and Ivar Enge published a study in The British Heart Journal in 1973 which reported: “No significant correlation was found when total coronary arterial score was correlated to serum cholesterol values or to triglycerides.”[11]

Not only is there strong evidence to show that serum cholesterol levels have no link to atherosclerosis, but there is also strong evidence to suggest that high cholesterol consumption does not raise blood cholesterol levels. The Framingham Heart Study, which set out to prove that eating more cholesterol in your diet increases your blood cholesterol levels, in fact showed that there was minimal difference in the blood cholesterol levels of the subjects despite subjects consuming cholesterol in widely varying amounts. [12] Scientists working on the Framingham Heart Study also studied the intake of saturated fats but eventually concluded: “There is, in short, no suggestion of any relation between diet and the subsequent development of CHD in the study group.”[13] It is difficult to stress the importance of this finding enough: there was no connection found whatsoever between diet and the development of CHD.

Further evidence that eating a diet high in saturated fat does not lead to CHD was published in The American Journal of Clinical Nutrition in 1981. The study compared the diets of two populations of Polynesians living on atolls near the equator. It also assesses the effect the diets have on the serum cholesterol levels in the populations. One of the populations, the Tokelauans, obtained a very high percentage of energy from coconut (high in saturated fat) compared to the Pukapukans, 63% compared with 34%. The Tokelauans had serum cholesterol levels 35-40mg higher than the Pukapukans. However , “vascular disease is uncommon in both populations and there is no evidence of the high saturated fat intake having a harmful effect in these populations.”[14]

Taking all these studies into account, it would appear that not only does having a high serum cholesterol level not have any connection to CHD, but that a diet high in cholesterol does not lead to high blood cholesterol levels and that a diet high in saturated fat does not have any link to CHD.

One final argument used to support the Lipid Hypothesis is the apparent effectiveness of statins in treating CHD. If, so the argument goes, statins reduce levels of serum cholesterol and they also reduce the risk of CHD, then reducing serum cholesterol levels must be the reason for the lower incidence of CHD. However, this reasoning contains two fallacies: firstly it assumes that statins have been shown to reduce the risk of CHD, and secondly it assumes that lowering serum cholesterol levels is the only effect of statins that could lower the incidence of CHD.

Both of these assumptions are false. A study was carried out by the University of British Columbia, part of the not-for-profit Cochrane collaboration, which concluded: “If cardiovascular serious adverse effects are viewd in isolation, 71 primary prevention patients have to be treated with a statin for 3 to 5 years to prevent one myocardial infarction or stroke.”[15] Small mortality benefits from statins have been shown for high-risk middle aged men.[16], [17] However, these trends are not seen in women and the elderly.15, 16 Even an advertisement for LIPITOR (atorvastatin calcium), one of the best-selling statins in America, has a disclaimer which includes: “LIPTOR has not been shown to prevent heart disease or heart attacks.”[18]

For the small minority of people who are protected  by statins, there is another explanation. Statins have been repeatedly shown to act as “potent anti-inflammatory” agents in patients with cardio vascular disease[19]. The reason for their effects in reducing incidence of CHD could be due to those effects rather than the reduction of serum cholesterol levels. This means that it is innappropriate to use the limited protection against CHD by statins as evidence for high serum cholesterol levels being a cause of CHD.

Gathering together the arguments made in this essay, we can conclude that it is very likely that there is absolutely no causal correlation between high cholesterol, either in the serum or in the diet, and CHD. Nor is there any causal correlation between a diet high in saturated fat and CHD. The emphasis placed on the Lipid Hypothesis by the government and other organisations concerned with public health is potentially due to the inital panic after the publication of Keys’ and Anitschkow’s studies. The feeling of urgency to act in order to prevent ever increasing numbers of deaths from CHD led to premature acceptance of the Lipid Hypothesis without sufficient evidence. The long term effect of this view has been the demonisation of diets high in saturated fat and cholesterol without sufficient justification from otherwise reputable organisations for the past thirty years.

Word count : 2431 words

(excluding title, name, biliograph and references)

Bibliography

“Trick and Treat” (Barry Grroves,2008)

“The Great Cholesterol Con” (Dr Malcolm Kendrick, 2007)

“The Cholesterol Myths” (Uffe Ravnskov, M.D., Ph.D., 2000)

“Seven Countries: A Multivariate Analysis of Death and Coronary Heart Disease” (Ancel Keys, 1980, Introduction, p. 1-17)

KIM CRAMER, SVEN PAULIN, LARS WORKÖ, 1966. Coronary Angiographic Findings in Correlation with Age, Body Weight, Blood Pressure, Serum Lipids, and Smoking Habits. Circulation; 33:888-900

U. RAVNSKOV, 2002. Is Atherosclerosis caused by high cholesterol?. Q J Med; 95:397-403

Prevention of Coronary Heart Disease. British Medical Journal , 21 September 1968; No. 5620, p.689

Sigurd Nitter-Hauge, Ivar Enge, 1973.  Relation between blood lipid levels and angiographically evaluated obstructions in coronary arteries British Heart Journal. 35, 791-795.

J. R. CROUSE, J. F. TOOLE, W. M. MCKINNEY, M. B. DIGNAN, G. HOWARD, F. R. KAHL, M. R. MCMAHN, G. H. HARPOLD, 1987. Risk factors for extracranial carotid atherosclerosis. Stroke; 18:990-996

Mukesh K. Jain, Paul M. Ridker, 2005. Anti-Inflammatory Effects of Statins: Clinical Evidence and Basic Mechanisms, Nature Reviews Drug Discovery 4. 977-987

Ian A. Prior, M.D., F.R.C.P., F.R.A.C.P., Flora Davidson, B.H.Sc., Clare E. Salmond, M.Sc., and Z. Czochanska, DIP.AG., 1981. Cholesterol, coconuts, and diet on Polynesian atolls: a natural experiment: the Pukapuka and Tokelau Island studies. The American Journal of Clinical Nutrition 34, p. 1552-1561.

Kannel WB, Gordon T., 1970.The Framingham Diet Study: diet and the regulations of serum cholesterol (Sect 24). Washington DC, Dept of Health, Education and Welfare.

J.C. PATERSON, M.D., LUCY DYER, M.Sc. and E.C. ARMSTRONG, M.D., London, Ont., 1960. Serum Cholesterol Levels in Human Atherosclerosis. Canad. M. A. J., 1960, vol. 82

Scandinavian Simvastatin Survival Study Group, 1994. Randomised trial of cholesterol lowering in 4444 patients with CHD: the Scandinavian Simvastatin Survival Study (4S). Lancet; 344: 1383-1389

Kalle Maijala, 2000. Cow milk and human development and well-being. Livestock Production Science 65 1–18

Daniel Steinberg, 2004. Review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy: part I, The Journal of Lipid Research, 45, 1583-1593.

GOFMAN, J.W.;LINDGREN, F.; ELLIOT, H.; MANTZ, W.; HEWITT, J.; STRISOWER,B.; HERRING, V.; LYON, T.P., 1950.The role of lipids and lipoproteins in atherosclerosis,  American Association for the Advancement of Science  Vol. 111pp. 166-171; 186

National Service Framework for Coronary Heart Disease – Modern Standards and Service Models, March 2000.

http://www.nhs.uk/conditions/cholesterol/pages/introduction.aspx

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001224/

http://www.health.gov/dietaryguidelines/dga2000/document/choose.htm

Figure 1: Daniel Steinberg, 2004. Review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy: part I, The Journal of Lipid Research, 45, 1583-1593.

Figure 2: Kalle Maijala, Cow milk and human development and well-being, Livestock Production Science 65 (2000) 1–18

Figure 3: J.C. PATERSON, M.D., LUCY DYER, M.Sc. and E.C. ARMSTRONG, M.D., London, Ont., 1960. Serum Cholesterol Levels in Human Atherosclerosis. Canad. M. A. J., 1960, vol. 82


 

[1] http://www.health.gov/dietaryguidelines/dga2000/document/choose.htm

[2] http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001224/

[3] Daniel Steinberg, 2004. Review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy: part I, The Journal of Lipid Research, 45, 1583-1593.

[4] GOFMAN, J.W.;LINDGREN, F.; ELLIOT, H.; MANTZ, W.; HEWITT, J.; STRISOWER,B.; HERRING, V.; LYON, T.P., 1950.The role of lipids and lipoproteins in atherosclerosis,  American Association for the Advancement of Science  Vol. 111pp. 166-171; 186

[5] “Trick and Treat” (Barry Groves, 2008, p.61-62)

[6] “The Cholesterol Myths” (Uffe Ravnskov, M.D., Ph.D., 2000, out of print – available at: http://www.ravnskov.nu/myth4.htm)

[7] “Trick and Treat” (Barry Groves, 2008, p.59)

[8] Kalle Maijala, Cow milk and human development and well-being, Livestock Production Science 65 (2000) 1–18

[9] Kalle Maijala, 2000. Cow milk and human development and well-being. Livestock Production Science 65 1–18

[10] J.C. PATERSON, M.D., LUCY DYER, M.Sc. and E.C. ARMSTRONG, M.D., London, Ont., 1960. Serum Cholesterol Levels in Human Atherosclerosis. Canad. M. A. J., 1960, vol. 82

[11] Sigurd Nitter-Hauge, Ivar Enge, 1973.  Relation between blood lipid levels and angiographically evaluated obstructions in coronary arteries British Heart Journal. 35, 791-795.

[12]“Trick and Treat” (Barry Groves, 2008, p.63)

[13] Kannel WB, Gordon T., 1970.The Framingham Diet Study: diet and the regulations of serum cholesterol (Sect 24). Washington DC, Dept of Health, Education and Welfare.

[14] Ian A. Prior, M.D., F.R.C.P., F.R.A.C.P., Flora Davidson, B.H.Sc., Clare E. Salmond, M.Sc., and Z. Czochanska, DIP.AG., 1981. Cholesterol, coconuts, and diet on Polynesian atolls: a natural experiment: the Pukapuka and Tokelau Island studies. The American Journal of Clinical Nutrition 34, pp. 1552-1561.

[15] “The Great Cholesterol Con” (Dr Malcolm Kendrick, 2007, p.164-165)

[16] “Trick and Treat (Barry Groves, 2008, p.52)

[17] Scandinavian Simvastatin Survival Study Group, 1994. Randomised trial of cholesterol lowering in 4444 patients with CHD: the Scandinavian Simvastatin Survival Study (4S). Lancet; 344: 1383-1389

[18] http://www.westonaprice.org/cardiovascular-disease/dangers-of-statin-drugs

[19] Mukesh K. Jain, Paul M. Ridker, 2005. Anti-Inflammatory Effects of Statins: Clinical Evidence and Basic Mechanisms, Nature Reviews Drug Discovery 4. 977-987