Saturday, 13 June 2015

The non-epidemic of stroke

The headline was in all UK newspapers on May 12th 2015.

It looks as though we are approaching something catastrophic - at least middle-aged men and to a lesser extent middle aged women. We are all of a sudden much more likely to have a stroke than was the case until very recently. This would be a true epidemic, almost like the appearance of AIDS almost thirty years ago. This is something very serious and we must be prepared. Could our hospitals and other components of health care cope? Should we all go out and obtain increasing sickness and life insurance?

What we should do is apply "olfacto-statistics" - does it smell right? Is there something a bit fishy?

Since 1960 there has been a progressive decline in the risk of stroke and in recent years there has been a much-reduced risk of stroke occurring in an individual. In other words the risk, the incidence has been reducing. On the other hand stroke is not usually immediately fatal and the effects can last for many years. The population is getting older - there are more middle-aged and elderly people, and therefore more people at risk of stroke. As a result there are within our population more people who have a had a stroke with disability due to it. In other words the prevalence has increased. This might have a big effect on health and rehabilitation services but it does not present a risk to an individual.

Stroke is the result of sudden impairment of the blood supply to part of the brain, which as a result does not function. The event is in medical terminology usually called "cerebro-vascular accident - CVA". Cerebral infarction would be a more accurate term. It is usually due to the blockage of an artery in the brain by the atherosclerotic process that also affects the coronary arteries of the heart, thereby causing a heart attack (myocardial infarction - MI). The incidence of both of these conditions has been reducing during the same time, as we have seen in a previous Post.

Ischaemia = reduction of blood supply; Infarction = tissue damage resulting from this

The other form of stroke of stroke is haemorrhage from spontaneous rupture of an artery within the brain, predisposed by an aneurysm that might be congenital. Haemorrhage has a higher mortality. It is particularly related to high blood pressure - hypertension. The treatment of this during the past forty years has contributes to a great decline in the incidence of cerebral haemorrhage.

Haemorrhagic stroke = cerebral haemorrhage

But what has happened that suddenly reverses this downward trend and dramatically increases the risk of stroke? There is as usual a clamour to jump to conclusions, to "round up the usual suspects" (as in Cassablanca).

And so the headline in the Times did not just report the headline news as appeared in the press relaese but also stated that this new epidemic is due to obesity and sedentary life - eating too much and exercising too little. We have seen in a previous Post that contrary to what we are all told, evidence indicates that mild and moderate obesity gives a survival advantage over the thin. The conclusion of the Times was not justified: there has been no sudden epidemic of obesity that would have led to such a sudden epidemic of stroke.

The story does smell a bit fishy, it does not make sense. It requires careful evaluation, and this was provided by the excellent BBC Radio 4 programme, "More or Less". This is a regular programme that looks at statistical statements and checks them for truth. In the edition of May 15th 2015 (available as a Podcast) it called to give evidence Tony Rudd, the National Clinical Director for Stroke NHS England. His information was that there was no epidemic: the incidence of stroke in middle-aged people is continuing to decline after all!

This can be seen in the two Figures. The first shows the decline since 1950, in this example in the USA, although the timeline has been similar in the UK. The second shows more recent years, this time in the UK. The decline, which indicates risk to the individual, has been dramatic. Although medical professionals tend to assume that the decline has been due to medical intervention, there might be some truth in this but it is likely that most of the decline has been "natural", for reasons unknown. It can be seen that the decline in stroke deaths occurred earlier than the end of the epidemic of coronary heart disease (CHD).

Percentage change year by year in death rates from stroke and coronary heart disease (Stamler, 1985)

Deaths from stroke per 100,000 since 1970 - UK, age-standardised
Source - British Heart Foundation

So where did the misinformation arise? Who made the press release that was taken up by all newspapers and given prominent headlines?

The answer is the Stroke Association, a well-meaning body that supports and represents those suffering from or or who have died as the result of stroke. To achieve this end, and to raise money to help sufferers and research, it wishes to achieve the maximum publicity. And this it did, most successfully. A large proportion of the population will have read the headline in most national newspapers, but very few will have listened to BBC Radio 4 More or Less, and therefore will remain unaware of the truth. The announcement will contribute to national anxiety. No retractions of the headlines appeared in the newspapers.

The truth is this. The Stroke Association was referring to hospital admissions, with perhaps suspected rather than proven stroke. This produces imprecise evidence. Death certificates are more accurate, but even then there are errors. Health statistics must always be treated with caution. Death rates from stroke have been falling progressively since 1960 and any reversal of this would be the result of something very serious and very new.

In recent years we have seen a move to minimise the effect of a stroke by the process of thrombolysis. This is the "clot-busting" treatment that has been used in the treatment of myocardial infarction since the 1980s. It is reasoned that if a stroke is the result of a blood clot occurring on a severe atherosclerotic lesion then the clot should be dissolved as soon as possible with restoration of blood flow to the brain. The challenge is immediacy, treatment with thrombolysis given within four hours and ideally within one hour of the onset of symptoms. It as also important for an emergency CT or MRI brain scan to be performed beforehand, so as to exclude the possibility of the stroke being the result of a haemorrhage. Thrombolysis would be catastrophic in this circumstance.

To achieve this the population has been encouraged to attend a major hospital immediately if the there is any suspicion of a stroke occurring. The diagnostic acumen of most people is not high and so most people admitted to hospital with what they think might be a stroke will not have had one. The timelines shown in the figures indicate deaths. The diagnosis rate in non-fatal cases, as with many disease, can change with the behaviour of patients and also the behaviour of doctors.

The CT scan has been used routinely in stroke patients for about 20 years. In the more common stroke due to blockage of an artery the early CT scan has usually been normal. This causes confusion to patients and families, but the purpose of the scan was to exclude haemorrhage (shown above) as it would be unwise to give even aspirin to a patients who has had a brain haemorrhage. In very recent years the MRI scan has been used. This has much higher sensitivity and often shows abnormalities in even "normal" people (volunteers). Although these abnormalities can be "false positives", in people with symptoms they might be interpreted as evidence of stroke. This will cause an increase in diagnosis rate of stroke, whereas the abnormality would previously not have been detected and a diagnosis might not have been made. There is concern about the overuse of MRI scans without critical evaluation of the findings.

We can see why there is an apparent epidemic of stroke. As with many present-day epidemics it is an epidemic of behaviour change and not an epidemic of disease. Careful evaluation is essential.

Headlines in the newspapers can be bad for your health.

Tuesday, 19 May 2015

When you are older, high blood cholesterol is a good thing

The elderly paradox –

when you are older, high blood cholesterol is a good thing

Conventional wisdom, which is very influential but almost entirely wrong, tells us that Coronary Heart Disease CHD is effectively self-induced, by eating the wrong foods in particular. The diet-cholesterol-heart hypothesis is challenged only by a few, who are considered to be heretics. In era of preventative medicine, the key to identifying individuals at particularly high risk of CHD is cholesterol screening.

This works on the basis that a high serum cholesterol level is an indicator of cardiovascular death, but the evidence to support this is weak. Like all population screening exercises, the identification of high cholesterol will always produce considerable anxiety in the individual; it will always give someone something else to worry about. Before creating national or even international anxiety (and it is already too late) it is as well to make certain how useful the serum cholesterol level of an individual is for predicting the future – we need to look critically at its predictive value.

The early work of relating serum cholesterol to future risk was undertaken using working men as the subjects. However only about 30% of those suffering from a heart attack fall into this age-group and the majority are above the age of 70 years. Is it reasonable to assume that what is found in middle-aged men is equally applicable to the elderly?

Doubt concerning this has been present for some time. We have seen data emerging from the long-term study of CHD in the town of Framingham, Massachusetts, organised by the National Heart, Lung, and Blood Institute of the USA. This is a unique study. A publication recording 30 years of follow-up was entitled “Cholesterol and Mortality” [1]. Its conclusion was quite remarkable and has been followed by what might be called a stunned silence:

“After age 50 years there is no increased overall mortality with either high or low serum cholesterol levels.”

I use the term stunned silence because this finding has received no publicity and has no practical impact whatsoever. Remember that about 90% of CHD presents after the age of 50 years. Think how many people above the age of 50 years have had their serum cholesterol level tested to try to predict coronary risk when it doesn’t.

Measuring the serum cholesterol of middle-aged men cannot be expected to provide any useful information but it seems to be unstoppable, especially when doctors receive a financial reward.

The Paris study

The relationship between serum cholesterol and survival has been investigated in a group of 92 women aged 60 years or more who were living in a nursing home in Paris [2]. The women were selected as being free of cancer as it had previously been recognised that serum cholesterol is low in people with cancer. They were followed up for five years and it was quite clear that those with the lowest serum cholesterol had the worst survival. 

We can see in Figure 1 the follow-up of people based on the blood levels of cholesterol. Here we are looking at the death rate. It is high, expressed as per 100 women as life expectancy is not good in such a group. However it is clear that the death rate is the highest in those with the lowest cholesterol average 4.5mmol/L. The death rate in those with a serum cholesterol of 4.5mmol/L was five times that of the death rate in those with high cholesterol levels.

Figure 1 - Paris
The relationship between death rate and serum cholesterol turned out to be what is called U-shaped, or J-shaped if asymmetrical, shown in Figure 2. 

Figure 2 - Paris

The optimum serum cholesterol in this group of women was 7mmol/L, representing those with the lowest mortality rate, standardised as 1. Those women with serum cholesterol greater than 8mmol/L had a slightly higher death rate. However those with lowest serum cholesterol had by far the highest death rate of all. It looks as though a cholesterol level of between 6 and 8 is ideal for women aged 60 or more. This is based on evidence and not dogma.

We can see that the death rate, that is the risk of dying, increased with increasing age as would be expected. The important and unexpected fact emerging from the figure is the highest death rate in those with the lowest serum cholesterol; this is the elderly paradox. The other way to look at the same thing is to record the number or percentage surviving.

The evangelists of the diet-cholesterol-heart hypothesis might argue that the reason for the high death rate in those women with low serum cholesterol is that they were dying of cancer, but this possibility was eliminated as far as possible at the start of the study. The authors comment that cancer mortality declines after the age of 70 years, and during the five-year follow-up during which 53 of the 92 women died, autopsy revealed cancer to be the cause of death in only one.

Another interesting result, and again paradoxical, is that at the onset of the study the average serum cholesterol of women known to have CHD was 5.9 mmol/L. In those who were not known to have CHD, cholesterol was higher at 6.3mmol/L.

The New Haven study

A further study of the elderly was undertaken in New Haven, Connecticut [3].  This was a community-based study of 997 persons aged more than 70 years with follow-up for four years. The CHD mortality was once again paradoxical in that a higher level of serum cholesterol was associated with a lower death rate (Figure 3).

Figure 3 - New Haven

The women studied in Paris were in residential care and would have been frail with poor life expectancy (they would have lacked what is called "physiological reserve", not easily measured). Those studied in New haven were not in supported care and the mortality rate was lower. However the important observation was that those with the lowest cholesterol levels had the highest mortality rates, again five times the mortality rate of those with the highest cholesterol levels. Over the age of 70 it is clearly an advantage to have a blood cholesterol level greater than 6.2mmol/L.

The Honolulu study

A similar result came from the Honolulu Heart Program, a study of 3572 men aged 71 to 93 years[4]. There are two ways of looking at the data. Rather than death rates, the Figures 4 and 5 show survival over a period of six years in four groups (quartiles) based on serum cholesterol. 

Figure 4 - Honolulu

Those with worst survival were those with the lowest cholesterol levels, mean 3.85mmol/L, and this is another example of the elderly paradox. Those with the highest cholesterol level (mean 5.99mom/L) had the best survival but at 6 years (Figure 5) all was equal - apart from the continuing poor survival of those with the lowest cholesterol. 

Figure 5 - Honolulu

The results were unchanged when first-year deaths were discounted, the purpose of this being to avoid the possible effect of low serum cholesterol and death being due to present but undiagnosed cancer.

Another interesting observation came out of this study. For the purpose of analysis, the subjects were divided into two groups, those with risk indicators of CHD (smoking, hypertension, diabetes or pre-existing manifestations of CHD) and those without. In both of these groups the mortality rate was lowest in those with the highest serum cholesterol.

In those with risk factors, the risk of death for those in highest cholesterol quartile (mean 5.99) was only 75% of those in the lowest quartile (mean 3.85). If we look at those without risk factors, those in the highest cholesterol quartile had only 56% risk of death compared to those in the lowest quartile. Clearly, in this age group above 70 years, low serum cholesterol cannot be regarded as a good thing. Why are we not told this?


It is worth noting some of the statements and conclusions of the authors.

“A generally held belief is that cholesterol concentrations should be kept low to lessen the risk of cardiovascular disease. However, studies of the relation between serum cholesterol and all-cause mortality in elderly people have shown contrasting results….Only the group with a low cholesterol concentration had a significant association with mortality…. We have been unable explain our results. These data cast doubt on the scientific justification for lowering the cholesterol to very low concentrations in elderly people.”

It is difficult for medicine and society to absorb the observation that a low serum cholesterol is associated with a worse health outcome but the evidence is strong.

The studies also indicate that there is much more to statin therapy than lowering serum cholesterol. If statins are to be given then the prescription should not be based on cholesterol measurements. There is no necessity to measure cholesterol levels in women and in men above the age of 50 – that is the benefits will not be for those tested, but for the doctors, the pharmaceutical companies and the academic departments that they support.


1.   Anderson KM, Castelli WP, Levy D. Cholesterol and mortality: 30 years of follow-up from the Framingham study. JAMA 1987; 257: 2176-2180.
2.   Forette B, Tortrat D, Wolmark Y. Cholesterol as risk factor for mortality in elderly women. Lancet 1989; 333: 868-870.
3.   Krumholtz HM, Seeman TE, Merrill SS, et al. Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. JAMA 1994; 272; 1335-1340.
4.   Schatz IJ, Masaki K, Yano K, et al. Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet 2001; 358: 351-355.

Tuesday, 7 April 2015

Why does the UK have General Practice / Family Medicine?

Why does the UK have General Practice / Family Medicine?

King Henry VIII, who granted Charters to the Universities of Oxford & Cambridge, and also to the Royal College of Physicians of London

The pattern of medicine varies little around the world. There are doctors, nurses, hospitals, and community health centres or offices.

Doctors work in hospitals as specialists, in the UK they are called consultants. Such specialists can also  work outside the hospitals, usually in an office where they see only ambulatory patients. In the UK, virtually all specialists work in hospitals and very few are purely community based. In other countries most specialists will be community based.

The most simple form of funding of medical care is via direct payment from patient to doctor. This might minimise surveillance by tax authorities, but it also means that access of the sick to health care is determined by their ability to pay.

Health insurance means that people pay into a fund when they are well and working and use that fund to pay for health care costs when needed. Flat rate insurance, typical of “private insurance”, means that everyone pays the same irrespective of income, and premiums are likely to increase with age. Exclusions for cover are common. 

Otto von Bismark

In advanced economies, especially those with well-developed taxation systems, it becomes possible to link insurance payment to income, and this becomes the basis of “social insurance”. The unemployed, children, and the retired will have health care free, paid out of the fund collected from those at work. 

Social insurance was first introduced by the German Chancellor Otto von Bismarck towards the end of the 19th century. It was popular and “just” and it became the pattern throughout Europe.

In the UK the organisation of health care was different. The postgraduate training “system”, like in other countries, was to produce specialists who would work from an office consulting room and also in hospitals. They were based mainly in London but later in other major cities. Harley Street became the centre of medical consultation.

Pendle Hill, from Clitheroe

This worked out quite well during the following years when medicine was not effective in therapy, although a great deal of learning was taking place. But the scene changed in the early 19th century with the development of the Society of Friends, the Quaker movement within Christianity. This movement started in the dales of the north-west of England. It was particularly associated with Pendle Hill, very close to where I live. Education was favoured by the Quakers but as they were not not members of the established church, the Church of England, they were excluded from the universities of Oxford and Cambridge by virtue of their Charters, which were granted by King Henry VIII in the 15th century. 

The university education of the Quakers had to be provided overseas, in respect of medical education particularly at the University of Leyden in The Netherlands, a city university not a state university. Later the medical graduates of this university set up a medical school in Edinburgh.

But Quaker doctors graduating in Leyden, and in Edinburgh, remained excluded from the Royal College of Physicians of London, also by its Charter granted in the 15th century. This exclusion had an important consequence as the hospitals of England used the  fellowship of the Royal College as a requirement for the appointment of medical specialists so as to ensure quality. 

Quaker doctors, were therefore unable to obtain hospital staff appointments, and so they developed community based medicals services. This was a very important development away from the cities, and especially in the sparsely populated areas of the Yorkshire Dales.

And so General Practice, family medicine, was founded, and as it was so useful to the population it became widely established across the UK. But because of the accidents of the political history restricted to the UK, there was no necessity for it to develop at the time in other countries. However family medicine has been introduced in many countries in recent years as it is felt to be both effective and economic.

David Lloyd George

Payment for general practice care was initially by the sick at the time of illness, but most GPs adjusted this according to ability to pay. Many introduced a pre-payment system, a simple form of insurance which meant that the sick did not need to pay a health charge at the time of illness. In 1911 David Lloyd George, at the time the Chancellor of the Exchequer of the UK government, introduced social insurance for general practice care and it has continued since then. It is based  on  the payment for GPs being a capitation fee, a sum of money paid annually for each patient cared for by a given GP (on the "list"), irrespective of illness and frequency of visits. Hospital doctors vetoed the proposal to include hospital care as part of social insurance.

GPs have become very much the cornerstone of preventative medicine, and family medicine has become much more than simply treating the sick. General Practitioners now have a great responsibility for controlling the budget of the NHS, including the financial allocation to hospitals.

More detail on this subject and an understanding of why the UK has an NHS will appear in an eBook, to be published shortly.

Tuesday, 31 March 2015

The sun has some benefits - NICE

The advice from the National Institute for Clinical and health Excellence (NICE), included advice on how to avoid skin cancer. This was published in 2010 and indicated that we must avoid all exposure to the sun, that we should apply a high factor sun barrier cream before going outside, to be repeated at regular intervals during the day if outside, and also to wear a hat and clothes that do not allow ultraviolet light penetration.

Observation of our fellow citizens would suggest that only a few people follow this advice, and such people will be relieved to hear that NICE has relaxed its advice.  The full report is not due revision until 2017 but NICE recognises that since 2010 a great deal of information has appeared concerning the importance of the sun to human health.

The NICE report of 2010 was based on advice from dermatologists, and obviously the thrust of the advice was avoidance of damage to the skin by the sun. We all know that the sun is essential for life on Earth. Sunlight is essential for plant growth and therefore directly and indirectly for all our food. It is essential for all our energy sources apart from nuclear and tidal energy (the sun is necessary for tides but by its gravitational effect and not by its radiation). 

The sun is not new and mankind has managed to survive because of it and with it for thousands of years without the advice from NICE. The population of the Earth is booming and there does not appear to be a major problem. But a small proportion of the population has a white skin and this is susceptible to damage from radiation from the sun. It is interesting to note that people with sun damage to the skin, including non-melanoma cancers on the face and head, have on average the best health and survival.

We know that white skin is particularly susceptible to sunburn and it is very important to avoid sunburn as it can be very unpleasant. When your shadow is shorter than your height, there is a danger of sunburn. Keeping in the shade is sensible, and also covering the skin with clothes. Otherwise protection creams should be used if exposure to the sun is prolonged, and especially if at a high altitude.

However NICE now agrees with common experience, that exposure to the skin without producing burn is not dangerous but is beneficial to our health.

There is an acceptable “physiological erythema”. This is transient redness of the skin produced by solar radiation but it different from and does not lead to burn. It will produce skin tan and vitamin D but it will not result in pain. Sunburn is painful but redness need not be. Similarly a hot bath might produce transient redness of the skin but this is not the same as a scald.

So now it is official: the sun is not as dangerous as was stated by NICE in 2010. Exposure to the sun is to be encouraged but sunburn is to be avoided.

Tuesday, 24 February 2015

CFS, ME - now SEID

Chronic fatigue syndrome CFS or Myalgic encephalomyelitis ME

This has always been a controversial illness. It has been recognised medically for only about forty years, but it is still not universally accepted by doctors. There is always the suspicion that it is somehow imaginary, that the sufferers might be frauds.

A new name has recently been suggested in the USA and I think this is a good move. The new name is Systemic Exertion Intolerance Disease - SEID.

I have had a clinical I interest in fatigue syndromes for more than twenty years. I just happened to see sufferers, but see them with an open mind as many doctors had not taken them seriously. I listened carefully to their stories (the basis of clinical medicine, as I had been taught) and a pattern seemed to emerge. I ultimately became the consultant lead within Lancashire and south Cumbria in the north-west of England, with a population of 1.5 million. The condition is rare but I gained great experience and saw more than 400 sufferers from CFS as I called it then. I learned from the patients.

The patients would report that they felt "tired", "exhausted", or "fatigued", hence the development of the term chronic fatigue syndrome. But normal observers would often say: "But I feel tired / exhausted / fatigued as well, implying that the patients / sufferers were frauds or malingerers, that they were effectively normal but just used a medical escape from work or domestic responsibilities.

It is true that normal people can feel tired, exhausted, fatigued. The problem was that the sufferers did not have the language to express what they were experiencing. There was not a suitable non-medical term that could be used - at least in English but I have no information concerning other languages.

The pattern is that the muscle and the brain are affected. Heart, liver, kidneys, intestines, blood production and other organs function normally. But the muscle do not. In very severe cases the muscles are not strong enough to support the body sitting in an upright position for more than a a few minutes, with the necessity of lying down, but this would be extremely rare. Usually maintaining a supported sitting posture would be satisfactory, but standing for more than a few minutes would be impossible. Walking for more than a few steps or a short distance would similarly not be possible. If at this point the sufferer would be unable to sit down then collapse would occur. The problem is clearly that of "exertion or exercise intolerance" or "exercise-induced muscle weakness". Once such a term is used, the nature of the illness becomes clear.

There is another illness characterised by exercise-induced muscle weakness, and that is myasthenia gravis. It is different and rather more dramatic. Double vision, drooping of the eyelids and slurring of speech are typical.

In SEID / CFS / ME brain function is also disturbed. This is a failure of concentration and the recording of memory. Conversation becomes very exhausting. Reading a book is impossible: when the bottom of the page has been reached, what was at the top of the page has been forgotten. Storylines of television or films cannot be followed.

We can see the advantage of the new term  Systemic Exertion Intolerance Syndrome. "Systemic" implies a wide-spread illness with perhaps more than one body system involved (muscles and brain. Exertion or exercise intolerance is now self-explanatory. The use of the term "Disease" is interesting, but it does give significant medical acceptance of the condition.

In general I use the term "disease" to describe an illness in which there is an obvious abnormality of anatomy, the structure of the body. This would include cancers, heart attacks (myocardial infarction), pneumonia and many others that we know. A "disorder" can be viewed as an illness in which part of the body does not function in a normal way but the structure appears to be normal. We use the term functional bowel disorder as an alternative to irritable bowel syndrome. But when we understand the biochemical aspect of a condition, such as a high blood sugar in diabetes, we tend to use the term disease. I have usually viewed SEID / CFS as a "disorder" as the muscle biopsies usually show normal appearances and the pathophysiology, the nature of the abnormal function, is not clear.

But with SEID there is some understanding of the nature of the disturbance within the body.

This will be the subject of another post shortly.

Tuesday, 10 February 2015

High cholesterol may not be bad for you - lesson from the liver

Primary biliary cirrhosis

Continuing the theme that the misinformation that we are given that cholesterol is somehow toxic is wrong....

By "toxic" I mean that a chemical substance that causes damage to us in a way that is related to dose and time-span of exposure. We are told that he greater the amount of cholesterol in the blood, and for a longer period of time, the more damaging it is. This assertion is not just over-simplistic but it is in defiance of the evidence. It is clear but generally unstated that it is only in men below the age of 50 that blood cholesterol is an indicator of risk of future manifestations of coronary heart disease (CHD). Above the age of 60, the age after which the vast majority of the deaths from CHD occur, a high blood cholesterol is a positive indicator of better survival.

Therapy is aimed at reducing the cholesterol level in the blood, but can this really be expected to be of any benefit? It does not appear to help.

Nature supplies us with a natural experiment by which we can investigate the effect of a high level of cholesterol in the blood. It is a liver disease called primary biliary cirrhosis (PBC).

PBC is a chronic disease of the liver that affects mainly middle-aged women. It has nothing to do with alcohol. The cause is unknown but it is generally classified as an auto-immune disease. In older women it tends to be a curiosity that is picked up incidentally from "routine" blood tests, but in younger women it is likely to be progressive and serious. There is no cure for this condition but it might lead to liver transplantation.

In PBC there is characteristically a very high level of cholesterol in the blood, and this has been recognised for more than half a century. This has given plenty of time for research.

The large amount of cholesterol in the blood in PBC might be deposited in the skin, creating fat patches that are called  xanthomas, or xanthelasma if there are many of them. They tend to occur on the inner parts of the eyelids, on the knees and in the creases of the palms of the hands.

According to what we are told this would make people with PBC particularly susceptible to early death from CHD. They might be expected to have a large amount of cholesterol deposited in the walls of the arteries causing blockage, but this does not happen.

People with an exceptionally high level of cholesterol can be recognised as having familial hypercholesterolaemia (FH), of which we learn more in a Post to follow shortly. It is however interesting to compare the fortunes of those with PBC and those with FH as both have similarly high levels of blood cholesterol.

Those with PBC have a fundamental disadvantage in that they have a serious liver disease. It is only in recent years that liver transplantation has become available as otherwise the younger ones would die early because of liver failure. Transplantation has proved to be every effective in this condition although it can sometimes recur in the new liver.

During the 20th century people with FH have been at a considerable disadvantage in respect of CHD with premature death. However it is now clear that in contrast people with PBC are not at any disadvantage. They do not develop premature CHD and this has been demonstrated in a number of studies. The conclusion of one study is that "(in people with primary biliary cirrhosis) marked hypercholesterolaemia not associated with an excess risk of cardiovascular disease."

If CHD were due to a high blood cholesterol with simple deposition of cholesterol from the blood then we would expect people with PBC to be very much at risk. But we can see that this is not so. This natural experiment casts serious doubt on the widely-accepted model of CHD. It indicates that CHD is not simply due to large amounts of cholesterol in the blood being deposited in the tissues.

We have seen in a recent Post that cholesterol in the wall of the arteries is not the result of simple deposition from the blood. It is an integral part of body defence mechanism and an important part of the inflammatory reaction.

Longo M et al.
Hyperlipidaemic state and cardiovascular risk in primary biliary cirrhosis.
GUT 2001 51 265-269.

Wednesday, 14 January 2015

What is the purpose of cholesterol?

We all know about cholesterol and we are all told that it is very bad for us. We are given the information that "the less of it the better", but we have seen in a previous post that this is not true in respect of women and in men above the age of 50. Above the age of 70, it is good for us, "the more the better".

Ancel Keys (1904–2014)
This means the blood level. It is assumed that this is derived from the diet and we have been told for more than half a century to avoid foods that contain cholesterol.  This message originated from Ancel Keys, the leader of the Seven Countries Study. We have seen this in a previous Post. It was not good quality research and it is said that the conclusion was decided before the study took place. Keys became a very successful evalangelist of fat and cholesterol avoidance, and he and his wife wrote books on the subject. His influence was remarkable but unfortunately wrong.

To avoid fat and cholesterol in the diet is of no health benefit. The reality is that cholesterol is synthesised within the body, something that was not considered by Keys.

This raises a problem: why should the body produce a substance that we are told is very dangerous? It would appear to be a great error of evolution, but this makes no sense. Cholesterol must have a benefit and perhaps the idea that cholesterol is bad for us is not correct.

Uffe Ravnskov b 1934

There is one person who has been almost a lone voice in trying to bring about an understanding of cholesterol. He is Uffe Ravnskov (b 1934).

Uffe was born in Copenhagan in 1934 and practised medicine in Sweden. In recent years he has been an independent researcher and most certainly independently minded. He has given the function of cholesterol a great deal of thought and has added a great deal to our understanding. I have been very impressed by his work and his ability to think differently from the main-stream.

It has been identified elsewhere that people with a high blood cholesterol have a health advantage. Firstly in the age group above 70 years on average the higher the cholesterol the greater the survival. It has also been identified that people with a high cholesterol have relative protection against AIDS, and also a reduced incidence of respiratory infections and post-operative infection complications.

LDL lipoprotein particle

LDL-cholesterol is alleged to be the "bad" cholesterol. LDL stands for Low Density Lipoprotein. This is not too important in itself but it is a combination of a fat (lipid) in the form of cholesterol and protein that enables its transportation throughout the body. It has been noted in the laboratory that LDL will neutralise bacterial toxins in serum.

These observations give more than a hint that the body is not in error in synthesising cholesterol because cholesterol is of considerable benefit. But what seems to be going wrong in coronary heart disease (CHD) and why is there a build-up of LDL-cholesterol in the walls of the coronary arteries?

CHD, like atherosclerosis in general, is the result of an inflammatory process within the walls of the arteries. This in turn is result of invasion of the walls of the arteries by micro-organisms. The 20th century epidemic appearance of CHD suggests that the cause has been a single micro-organism, possibly but not definitely Chlamydia pneumoniae,  but perhaps several micro-organisms are involved. Because of the obsession with diet and cholesterol, research into the role of micro-organisms in the development of CHD has been seriously neglected.

Treponema pallidum
There is however another micro-organism that gives rise to heart disease and arterial disease. It is a spirochaete, Treponema pallidum, the cause of syphilis, which a hundred years ago was a very major cause of disability and death. So do not take notice of people who tell you that CHD could not possibly be due to a micro-organism: it can be and it is.

Micro-organisms cause other forms of heart disease, disease of the valves of the heart. Streptococcus pyogenes causes rheumatic fever and as a result chronic disease of the mitral valve in particular. Rheumatic heart disease used to be very common, but not now.

Viruses can cause acute disease of the heart muscle, viral myocarditis.

Another infection of the heart is endocarditis, infection settling on the heart valves. A variety of micro-organisms are involved, in the past mainly Streptococcus viridans , which passes from the mouth into the blood-stream.

So there is no reason why a microbial cause of CHD should not be considered seriously.

The coronary arteries on the surface of the heart

When a micro-organism invades the wall of the arteries, then as in other parts the body, a defensive inflammatory process takes place. The first line of defence in the tissues is LDL-cholesterol and it accumulates very rapidly in response to the infection. The second line takes the form of large white cells called macrophages, the "big eaters". They clean up the inflamed tissues and ingest the cholesterol. This development in the walls of the arteries is called "atherosclerosis". Antibody reactions also occur and are very powerful.

As in other parts the body, such as skin and joints, an inflammatory process is associated with swelling and that is the case with CHD.  This is usually an advantage in terminating the disease, but sometimes there is just a controlling action, not curative. This is typical of chronic inflammatory and auto-immune diseases.

Atheromatous plaque in an coronary artery
The inflammatory process can be such that the activity of macrophages cannot keep up with LDL cholesterol deposition, itself a defensive process. Swollen patches called plaques then develop in the wall of the artery, and they obstruct the flow of blood. In a similar way inflammation in the throat of a small child can cause swelling and obstruction and the illness of “croup”. Also inflammation in the intestine of people with Crohn’s disease will produce swelling, which can cause intestinal obstruction.

In the coronary arteries it is "rupture" of the surface of the plaque with the formation of a blood clot that brings about a total obstruction to the artery. The result of this is a heart attack, myocardial infarction, often with sudden death. Statins can stabilise plaques, thus inhibiting disruption, acting through an anti-inflammaory process and not inhibition of cholesterol synthesis.

So we can understand that CHD is likely to be due to a micro-organism, this explaining why it has been an epidemic otherwise not explained, and that it clusters in families. It has been much more common in locations with poor sun exposure and low vitamin D levels, and also in other circumstances in which immunity is low (after chemotherapy or organ transplantation). The cholesterol deposited in the arteries is a result of the infection, the inflammatory process unfortunately obstructing the flow of blood.

As inherited immunity has developed within the population, so the epidemic of CHD has subsided and is almost at an end. It is however possible that similar epidemics will emerge in the future. If a microbial cause is accepted and the putative micro-organism identified, then protection through immunisation can be anticipated.