Sunday, 19 June 2016

Cholesterol controversy - June 13th 2016

Monday June 13th 2016

The UK national press, including radio and television, reported on Monday June 13th 2016 a “new surprise and controversy” in respect coronary heart disease and survival.

The report concerned a paper published in the British Medical Journal on-line edition. This was a meta-analysis of a number of previous publications  linking survival to blood levels of cholesterol. The conclusion was that above the age of 60 years a high level of cholesterol is not a danger but it gives a survival advantage. Although this was regarded as a controversy, it will come as no surprise to readers of this Blog as I have indicated this finding on previous occasions. 

Framingham

The most important cholesterol–survival study was in Framingham, Massachusetts, which I reported in a  post in December 2015. This was a highly detailed follow-up study lasting for thirty years, and it will never be repeated. The major concern was the large number of deaths from coronary heart disease (CHD) during the epidemic, with large numbers of premature deaths. Now that the epidemic has almost come to an end there is no incentive for further detailed epidemiological study.

Between 1951 and 1955, when the epidemic of CHD had become obvious and a serious public health problem, the study recruited 1959 men and 2415 women who were free of cancer and heart disease. They were between the ages of 31 and 65 years. They were followed in great detail for thirty years, at the end of which the conclusion was clear. For the purpose of data analysis the subjects were grouped into quartiles based on the blood levels of cholesterol.

In Figure 1 we can see that in men aged 31–39 there was a survival advantage in those with the lowest blood levels of cholesterol, 84% after 30 years, compared to those with highest cholesterol levels, only 68% after 30 years.

Figure 1. Survival of men aged 31–39, Framingham
It can be seen in Figure 2 that the overall survival for 30 years was much better in 30 year old women compared to 30 year old men. However in women of this age-group the survival advantage of a low blood cholesterol level was much less, 91% compared to 85%  for the highest cholesterol levels after 30 years.
Figure 2.  Survival of women aged 31–39, Framingham

In Figure 3 we can see that in men aged 56–65 survival was not influenced by the blood level of cholesterol. We can also see that at that time only about 10% of men aged 56–65 lived to the age of 90.

Figure 3.  Survival of men aged 56–65, Framingham



This conclusion was subsequently ignored.

The Framingham study did not not recruit people aged above 65 years, but other studies have done. I have previously reported the Paris study, the Honolulu study, and the New Haven study. 

Paris, Honolulu, New Haven

These studies all demonstrated something different. In the age group above the age of 70 years, those with the highest blood levels of cholesterol had the best survival. This can be seen in the survival curves in the Honolulu study, Figure 4, showing that those with the lowest blood levels of cholesterol had the lowest survival at 6 years.

Figure 4. Survival by cholesterol level. Honolulu

The conclusion of the Honolulu Heart Program was that "These data cast doubt on the scientific justification for lowering cholesterol to very low concentrations (<4·65 mmol/L) in elderly people".  

It would appear that no notice was taken of this study.

Similarly, as shown in Figure 5, in the Paris study, the worst survival was in those with the lowest blood levels of cholesterol. The study carefully and successfully excluded any person who had cancer, which could have contributed to both low cholesterol and death.

Figure 5. Survival by cholesterol level. Paris

There was a further study from New Haven, Connecticut, showing that cholesterol was not an indicator of cardiovascular risk in the elderly. The data is shown differently from the other studies. The end-point of the study was the percentage of those who died from CHD after four years. This was grouped on three blood level groups of cholesterol, for men and for women.
Figure 6 . Deaths from CHD at four years based on cholesterol level. New Haven.
We can see in Figure 6 that in the New Haven study of people over the age of 70 years, the CHD death rate was highest in men and women with the lowest blood cholesterol levels.The authors of the study (highly respected) state that the results do not support the hypothesis that high cholesterol is a risk factor for death or CHD death in older persons.

It is clear and it is not new that in people above the age of 60 years a high blood cholesterol is of no concern and if anything it is a good thing. But these results have been hidden from public view for a long time. Is is good that the information is now being brought to attention by the recent British Medical Journal publication. 

A high cholesterol is a good thing when you are above the age of 60


The conclusion that a high blood level of cholesterol (LDL-cholesterol) "may not cause heart disease in the elderly" and might be a good thing conflicts with “conventional wisdom”, led by pharmaceutical and academic vested interest. The misconception that cholesterol is bad fuels vast profits for the pharmaceutical industry and the academic departments that it supports (the main objective of these departments is the pursuit not of truth but of research funds).

There is no justification in testing the blood cholesterol level in people above the age of 60 years.

But what about statins?

As I have pointed out in previous Posts, the problem is that the small benefit of statins is nothing to do with the ability to lower blood levels of cholesterol. The so-called cholesterol experts always talk and write about “cholesterol-lowering with statins”. The clinical trials that they quote are trials of statin therapy, no more and no less. If we forget the cholesterol-lowering effect of statins then everything starts to make sense.

In response to the press release mentioned above (Daily Telegraph, June 13th 2016) was reported:

Professor Colin Baigent, an epidemiologist at Oxford University, said the new study had “serious weaknesses and, as a consequence, has reached completely the wrong conclusion”.

The study mentioned was not a clinical experiment or trial. It was a review of a number of observational studies of some size. The results were clear: high blood cholesterol in people above the age of 60 years gives a health and survival advantage. The conclusion in this respect is straightforward and to suggest that the study reached “the wrong conclusion” is absurd and a highly prejudiced comment: conclusions should follow a study and not precede it. 

I wonder if Professor Baigent ever read the monumental Framingham study, and if so did that 30 year study also reach “the wrong conclusion”?

And there was the quote of an absurd and automatic denial from the British Heart Foundation:

"There is nothing in the current paper to support the author's suggestions that the studies they reviewed cast doubt on the idea that LDL-Cholesterol is a major cause of heart disease or that guidelines on LDL reduction in the elderly need re-evaluating."

The article continues to quote Professor Baigent:

“[studies] have shown that lowering cholesterol using a drug does reduce the risk of heart disease in the elderly, and I find this more compelling than the data in the current study.”

This quotation from Professor Baigent introduces “a drug”, something that was not the subject of the epidemiological studies. A professor of epidemiology should know better than to mix an epidemiology study with a drug trial. Statin drugs do reduce death rate by a small amount in all age-groups, but as I repeatedly mention, this is nothing to do with cholesterol-lowering. The clinical trials alluded to were of statin therapy: cholesterol-lowering and other metabolic effects were not standardised or controlled.

The West of Scotland trial of statin therapy demonstrated after five years an absolute mortality reduction of 0.9% in men aged 65 years 4.1% in controls, 3.2% in treated group). As part of the analysis the participants taking the statin were divided into five groups based on the amount of reduction of blood cholesterol. For each of these groups the reduction of coronary events (compared to controls) was determined. When these were plotted together in a scattergraph, the result was as in Figure 7.


Figure 7. Statin effects - cholesterol reduction and coronary events
There was no association between cholesterol reduction and reduction coronary event rate. Surprisingly the reduction of events was greatest in those with no cholesterol reduction, but the significance of this is doubtful. The event reduction in the three groups with cholesterol reduction was effectively constant. The trend-line is close to flat.

Don’t forget that cholesterol-lowering with diet and medications other than statins (for example ezetimibe) has no effect on mortality: benefits are restricted to statins only. Let Baigent continue to support statin therapy, but accept that a high cholesterol above the age of 60 years is not a risk factor of CHD but has an advantage, as is demonstrated clearly.

Following the report in the Daily Telegraph, the usual denial from well-known diet-heart-cholesterol enthusiasts appeared in The Times a few days later.

The use of statins

We should simply forget about cholesterol. The use of statins should be regarded as an empirical prevention of CHD death. The prescription should be based on the sum of risk factors that must not include blood level of cholesterol, other than in men below the age of 50.


The article headline indicated that because a high blood level of cholesterol is good rather than bad, statins are a “waste of time”. This logic is not correct as statins are of some benefit, but that benefit is not connected to cholesterol. There is a different beneficial effect, probably an anti-inflammatory action. This is generally not appreciated or understood. 

Statins are of only a small benefit. In the first placebo controlled statin trial conducted in the West of Scotland, the subjects were men of age 65 with about the world’s highest incidence of CHD death. The death rate in the placebo group was 4.1% after five years, and lower in the group treated with pravastatin at 3.2%, an absolute reduction of 0.9%. This meant that 100 men had to treated for five years to prevent (delay) one death. The population mortality rate in Scotland at that time was about 850 per 100,000 per year. It is now only about 15 in the UK, a reduction of 98%. 

If we use the proportionate death reduction rate of 25%, we can expect that if undertaken today (not possible in practice) and given the much reduced death rate, the placebo group would have a mortality rate of .074% and the treated group .056%. This indicates that 7400 men would need to be treated in the same way to prevent 2 deaths. The price of preventing (delaying) one death would then be £675,000, much more in younger age-groups. So statins do help but only a little and the help is very expensive.

It is sad that highly qualified cholesterol experts are unable to separate cholesterol risk from statin benefit. Whenever anyone challenges the diet–cholesterol–heart hypothesis there is an immediate and thoughtless reaction to deny the challenge and to claim that the small success of statin therapy “proves” the highly flawed hypothesis (it proved nothing of the sort). Such an inevitable reaction was published in The Times on June 15th 2016.


Conclusion

It is clear from the observational studies that a high blood level of cholesterol in people above the age of 60 years does not constitute a cardiovascular risk, but on the contrary a survival advantage. This is not new and the suppression of this information must stop. Observational studies such as the Framingham , Honolulu, Paris, and New Haven studies are very  important. 

It is irresponsible of the authors of the Times letter, using impressive titles at the University of Oxford, to rubbish good quality observational studies, and completely ignore the findings of the highly-respected Framingham study and other studies. 

What has happened to scientific objectivity and analysis? 

Perhaps the answer is the pursuit of money. The diet–cholesterol–heart hypothesis is the goose that lays golden eggs, for the diet industry, the pharmaceutical industry, for academic departments, and for a large number of  national and international conferences.





Is the truth important? I think it is.


References:




Schatz IJ et al. Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet 2001; 358: 351-355.

http://www.thelancet.com/journals/lancet/article/PIIS0140673601055532/abstract



http://www.ncbi.nlm.nih.gov/pubmed/2564950



http://jama.jamanetwork.com/article.aspx?articleid=381733





Tuesday, 7 June 2016

The cause of disease and the discovery of ignorance

The discovery of ignorance – the cause of disease in the age of enlightenment.

Hooke's microscope
The presence of disease can be determined by examining individuals; this is the process of clinical medicine.

The cause of disease can be established by examining groups or populations; this is the process of epidemiology.

But all this is new.

Understanding the cause of disease

When I was five years of age I was ill with pneumonia. It was very serious and nearly fatal, but fortunately penicillin had just become available. The diagnosis was established by the doctors. My mother, like most people, was anxious to establish “the cause”, by which she really meant the reason. Like most people, she tried to explain "pneumonia" on the basis of one individual - me. 

Shortly before pneumonia
My mother was convinced that the cause of pneumonia (in my case) was that shortly before the illness, when I came home from playing outside on a winters day (remember that this was in the late 1940s, no television, no iPads etc) I had snow in my Wellington boots. Here lay the obvious cause.

My mother had no training in pathology and had no understanding of the concept of disease. But there might have been some truth in her understanding of my “illness”, as opposed to my “disease”. Without this mid-winter chilling event perhaps I would not have developed pneumonia. Perhaps this event made me susceptible to pneumonia, as I understand it with a training in pathology (disease process).

A disease is universal: it can happen anywhere. It is the same pathological process in all countries, even though its distribution and frequency can vary greatly. In respect of pneumonia we recognise a clinical syndrome of fever, shortness of breath, cough productive of sputum, perhaps chest pain related to breathing (pleurisy), occasionally abnormal findings on listening to the chest (auscultation), and abnormalities on chest x-ray. If it turns out to be fatal, then the autopsy will reveal further details of the actual pathology.

Susceptibility

But not everyone develops a disease. I was the only one of my friends who developed pneumonia, perhaps because the cold effect of snow in my boots increased my susceptibility to what is generally regarded as an infection of the lungs.

The illness of an individual is the result of the disease and its cause, but also one or more susceptibility factors. Another way of looking at this in more general terms is that the presence of disease is the result of cause together with susceptibility.

disease  =  cause  x  susceptibility

and

illness  =  disease  x  individual factors

There are many examples of this:

  • death in a road traffic accident is the result of impact, but susceptibility includes one or more drivers being under the influence of alcohol or drugs; 
  • AIDS is the result of exposure to HIV, but multiple sexual partners increases susceptibility;
  • hepatitis C virus (HCV) infection is the result of the virus with intravenous drug use increasing susceptibility.

Individual factors

There is a tendency to put too much emphasis on individual factors when considering why an individual becomes ill or dies, even if such a factor might be completely irrelevant, as judged by the experience of many other victims and an understanding of pathology. 

The world becomes full of amateur doctors with ideas of early death or long life based on extremely limited experience. When someone reaches the age of 100 or more years, there is often a news-reporter posing the question: “To what do you attribute your long life?” The answer will be something that the individual enjoys and especially a food, possibly cabbage. It is most unlikely that the answer will be “Good luck”, as we all think that we understand more than we do. There must always be "an explanation".

The role of God

Everything changed in the Age on Enlightenment, known in French as the Siècle des Lumières  (the Century of Enlightenment), and in German as the Aufklärung).

Although it started in the early 18th century, scientific foundations, the scientific revolution, occurred a century earlier. But it was in the Age of Enlightenment that the greatest discovery in human history came about, the discovery of ignorance.

Jean-Jacques Rousseau
Previously there was always an answer: divine control over all humans and their destinies. This was challenged by, in particular, Jean-Jacques Rousseau (1712–1778), the French-based philosopher who was born in Geneva. 

There are still many people today who believe with great conviction that the Lord watches over us and protects us all. The great challenge to belief comes when a good close friend or relation dies young, or when many innocent deaths result from famine or warfare. A further challenge occurs when it is found that beseeching God through prayer might not work. 

The Age of Enlightenment

But the traditional concept of a universe with the Earth at the centre and God in overall control became challenged by the 17th century observations of Copernicus, Galileo and Kepler. Newton’s studies of light indicated that our view of the world was over-simplified. Studies of human anatomy and physiology provided the foundations for the future understanding of disease.

The 18th century that followed was a time in which the standard answer to all questions, that it is “God’s will”, was questioned. The occurrence of disease was no longer the will of God, and divine retribution for misdeeds obvious or far from obvious. Blaming victims for their sins was no longer automatic. But sadly three centuries after the new age of enlightenment, victim-blaming is something that I hear far too often. The sins are now against man rather than against God.








The Discovery of Ignorance

I first learned of this concept when listening to Yuval Noah Harari being interviewed at the Hay-on-Wye Literary Festival in May 2015. Following this I read his remarkable book “Sapiens”.


Yuval Noah Harari
The discovery and acknowledgement of ignorance was such an important step in human evolution, and especially in the 17th and 18th centuries, but now it is almost forgotten. The astounding scientific developments of the 20th have created new gods in the form of scientists. We expect them to know everything, and this is the impression given by news broadcasts on so many days.

It is the same with doctors. They give the impression of knowing everything, and that is what patients and their families expect. They do not expect is their doctor to say “I do not know”. This is taken to be a shortcoming of the individual doctor and so the family will go on an often futile journey until they find a doctor who claims that she (most doctors are now female or shortly will be) does know.

But there is a difference in answering the question “What is the cause of my family member’s illness?” and “What is the cause of my family member’s disease?” The answer to the first question is the name of a disease or a syndrome. The doctor should be able to answer this question as it applies to an individual patient. But stating the cause of a disease is very different; it is answering the question on behalf of medical science as a whole. It is here that she (he) can say “Medical science does not know” rather than “I don’t know”. 

Studies of populations

It is difficult for people to accept that “the doctor does not know”, but it is often the case that “doctors do not know”, and this is acceptable if explained. But this leaves the vacuum of understanding that is filled by guesses based on little experience, often filled by alternative practitioners who do not base their “explanations” on the basis of objective and well-researched pathology.

With the Age of Enlightenment came attempts at understanding disease without invoking God. There were several epidemics of cholera in London in the 19th century, and they were generally assumed to be the result of “poisoned air”, not an unreasonable conjecture. However the physician John Snow (1813–1858) made observations (new investigative epidemiology) that led him to conclude (correctly) that it was the result of “poisoned water”.

The causes of disease

Girolamo Fracastoro
The germ theory of disease was first proposed by Girolamo Fracastoro (1475–1553), and it is fortunate he was not executed for such heresy. His idea was well ahead of its time and it was in the 1670's that the Dutch microscopist Antonie van Leeuwenhoek (1632–1723) discovered vast numbers of "little animals", previously unknown. 

This was soon confirmed by Robert Hooke (1635–1703), who recognised and was the first to use the term "cell" to describe the basic building block of life. Microbiology then developed into the exciting science that we know today. It has been epidemiology, microscopy and microbiology that have done more than anything else to develop our understanding of disease.

Robert Hooke
Antonie van Leeuwenhoek














Robert Koch
Robert Koch (1843–1910) recognised the microbial cause of tuberculosis (TB). During the previous century it was considered to be “constitutional”. This means inherited, part of the make-up of the individual. Inheritance is another major pillar of the understanding of the cause of the disease, also recognising that there is more to inheritance than genetics. Now in the 21st century we are starting to understand the importance of our inherited microbiome.





Coronary heart disease

The key to understanding is humility, and the start of knowledge is the recognition of ignorance. The application of these factors might enable us to understand the nature of coronary heart disease (CHD).

My recent Blog Posts have concentrated on CHD, identifying its epidemic nature, its sudden onset and its rapid decline. I have not discussed its cause. Despite the fact that it has been one of the most serious epidemics of all time and certainly by far the most serious epidemic of the 20th century, its cause is not known. 

This is not generally admitted, but it needs to be acknowledged. Ignorance is generally not admitted by experts.

Thoughts on the cause of CHD will follow shortly.



Monday, 2 May 2016

Coronary Heart Disease - the onset of the epidemic

The onset of the epidemic of coronary heart disease


I have indicated in several Posts that during the 20th century we experienced one of the most serious epidemics of all time, that of coronary heart disease (CHD). 

Some readers have commented why I seem to be unique in defining CHD as an epidemic, but I have indicated a more recent acknowledgement of the epidemic from the USA. There is however a tendency to view life, and death, as stable and unchanging, with no appreciation of the past. Memories tend to be short,which is why we need good written records.

An epidemic must have a clear onset, an increase to a peak, and then a decline. In respect of CHD we can identify a peak in about 1970 (slightly earlier in the USA), and there has been a well-documented decline. I have described this in previous Posts, identifying that the death-rate has declined dramatically. This has led to a great increase in the number of very elderly, these people having not died from CHD.

The purpose of this Post is to define the onset of the epidemic. Many people assume that CHD has always been present, but this is not the case. When I was working as a recently qualified doctor in the years 1966-72, it was clear that we were experiencing a large workload of a very major illness for which we not prepared and which was obviously new. The mortality rate was very high. About 50% of those experiencing myocardial infarction (MI) died almost immediately. Of those surviving to be admitted to hospital, up to 30% died during their stay in hospital.

The onset of the CHD epidemic

The detail of the onset is hidden away in the UK national death statistics, and these were analysed by Dr Maurice Campbell. His work was published in two excellent papers in the British Medical Journal in 1963, but they seem to have had little or no lasting impact. 

Dr Maurice Campbell, 1891–1973
Dr Maurice Campbell was a physician Guy’s Hospital, London. He was one of the pioneers of cardiology and became the first editor of the British Heart Journal (later renamed as Heart) He has been described as follows:

 “Physician, thinker, naturalist, and indefatigable worker Maurice Campbell adorns the splendid traditions of British medicine.”

A detailed account of Dr Maurice Campbell and his career is to found in the journal Heart. It was written by Dr Maurice Silverman, a consultant Psychiatrist colleague of mine for many years in Blackburn, UK. It makes interesting reading, giving a good account of Campbell’s major contributions to cardiology at the formative time of the introduction of cardiac surgery, specifically mitral valvotomy (the opening of a severely narrowed mitral valve).

Campbell examined very carefully, in what is said to be his usual style, the records of the Registrar-General of Births and Deaths of England and Wales, which started in 1838. The earliest records that Campbell studied were from 1876. Campbell’s two papers covered the two periods of 1876 to 1929 and 1929 to 1959.

He identifies that during the half-century of 1929 to 1959 a great deal of medical development had taken place. There was a much-improved understanding of disease process, of pathology. Consequently there was a refinement of medical diagnosis and of terminology. And therefore was a change in death rates from a given diagnosis the result of a change in disease incidence and fatality rate, or merely due to a change in nomenclature?

Campbell felt that this was probably the case during the period 1876 to 1929, as during that time the total number of deaths from heart disease remained the same, and perhaps there was just a change of terminology within this large group. Deaths from infectious diseases (including tuberculosis) were falling in the first years of the 20th century, and so the proportion of deaths from heart disease inevitably rose, but not the absolute number of heart deaths per year.

1876–1910

The data for this period comes from the Annual Report for 1910 and the Statistical Review for 1921.

Between 1876 and 1906 there was a steady decline in the overall death rate of the population, but the number of deaths from heart disease remained constant. It is obvious that the proportion of deaths from heart disease increased, but actual numbers are much more important than proportions and percentages. 

Figure 1: Death rates from all causes and heart disease, 1876–1910

The paper presented death rates per million per year, as from the data supplied by the Registrar-General, but in this and other Figures I have transcribed to deaths per 100,000, as is used today.

It is interesting to look at other aspects of changing mortality. Deaths from tuberculosis (TB, then known as “phthisis”) were falling. The reason for this is not clear as it was not until 1952 that specific treatment became available. Presumably the reduction of TB deaths was the result of improving nutrition, general health and therefore immunity of the population. Deaths from bronchitis were also falling, perhaps for the same reason. Deaths from pneumonia were increasing, perhaps a change of diagnosis from bronchitis. Deaths from cancer were increasing, perhaps due to improved diagnostic processes.

Figure 2: Death rates, 1876–1910

There was a slight decline in deaths from heart disease over the time period 1891 to 1910.

Figure : Death rates from diseases of the heart, 1891–1910


1911–1921

The data for this period comes from the Statistical Review for 1921 and the Statistical Review for 1931.

We still see little change. There was a slight increase in heart deaths during the First World War, for reasons not clear. This appeared to be the result of deaths from diseases of the heart valves (valvular heart disease, VHD), the result of earlier rheumatic fever that damaged in particular the mitral valve (this is situated between the left atrium and the left ventricle, and therefore damage severely impedes blood flow from the heart). The aortic valve could also be damaged in the tertiary stage of syphilis.


Figure 4: Death rates from diseases of the heart, 1911–1921

“Angina” was used in the heart disease classification for the first time. It is chest pain related to exercise and the result of narrowed coronary arteries, a manifestation of coronary heart disease (CHD). Angina can also result from severe stenosis of the aortic valve of the heart.

In the 1912 edition of his “Principles and Practice of Medicine” Sir William Osler commented that “It [angina] is a rare condition in hospitals: a case a month is the average even in the larger metropolitan hospitals.” 

Angina certainly was a rare cause of death, just 3 per 100,000 and with no change during the decade 1911-1921.

1922–1931

Campbell states: “When we come to this decade there is an enormous change.”

During this decade the number of deaths from all diseases of the heart rises significantly, from 156.8 to 253.5 per 100,000 per year. There is no increase in deaths from heart valve disease.


Figure 5: Death rates from diseases of the heart, 1922–1931
But during this decade we see something new, and in retrospect it is the onset of the epidemic of coronary heart disease. The data from the Statistical Reviews use the new term “coronary artery disease (CAD)” but this equates to the term “coronary heart disease (CHD)”, used by Campbell and in popular use today.

The increase of CHD deaths started in 1922-1924, but was most marked in the years 1927-1929.


Figure 6: Death rates from CHD (CAD), 1922–1931

It was in the 1920s that the pathologists described coronary artery atherosclerosis with surface thrombosis leading to myocardial infarction (MI), death of heart muscle resulting from interruption of its blood supply. This is what we generally now call a heart attack; a new disease of coronary heart disease (CHD) was thus identified. 

The clinical and pathological description of CHD had first been published in 1912 by James Herrick (1861–1954) in the USA, just case reports (he also first described sickle cell disease, which was known as Herrick's disease). He presented his paper at the meeting of the Association of American Physicians, but in his words "It fell flat as a pancake".

For several years few people took notice of Herrick's description of CHD, especially outside the USA, and in the UK it was not until the second half of the 1920s that further descriptions appeared. By this time the condition was becoming more common.  

A good clinical and pathological description was given by Carey F Coombs and Geoffrey Hadfield from the Bristol Royal Infirmary, published in the The Lancet in 1926. The authors acknowledged the description by Dr AG Gibson published in The Lancet just three weeks earlier. To quote the excellent and clear introduction by Coombs and Hadfield:

“Sudden or rapid occlusion of a larger brach of one of the coronary arteries of the heart by thrombosis or (much less often) by embolism initiates a certain series of symptoms which it is convenient to groups together under three heads: (a) acute [left] ventricular failure, (b) chronic cardiac failure, and (c) death before diagnosis.”

This description is perfectly appropriate today.

1932–1940

The changes of the previous decade continued. There was once again an increase in all heart deaths, from 231.6 to 341.6 per 100,000 per year. This indicates that there was a serious problem. There was a slight decline of deaths from valvular heart disease, and a considerable increase in deaths from CHD. The data from this period was taken from the Statistical Review for 1940.


Figure 7: Death rates from diseases of the heart, 1932–1940

The deaths from CHD are isolated in Figure 8, and show an impressive change. Between 1920 and 1940 the death rate had increased from 3 to 46.7 per 100,000 per year, sounding more impressive if expressed as a 15-fold increase, or 1500% increase. It is difficult to escape the conclusion that a serious epidemic was developing.


Figure 8: Death rates from CHD (CAD), 1932–1940

At this time we were in The Second World War. Casualties on the battlefield and in the bombed cities were more important than a change in the causes of death in the nation, no matter how serious in retrospect.

1941–1949

During this decade there was slight increase in deaths from heart disease, all causes, with a continuing decrease in deaths from VHD, and a continuing increase in deaths from CHD.


Figure 9: Death rates from diseases of the heart, 1941–1949

By 1949 death rate from CHD had reached 100 per 100,000 per year. The data came from the Statistical Review for 1949.

Figure 10: Death rates from CHD (CAD), 1941–1949

In view of the only slight increase in total heart disease deaths and small decrease in VHD deaths, Campbell suggests that the increase of CHD deaths might have represented in part an improving recognition of coronary heart disease.

1950–1959

During this decade the death rate from heart deaths all causes seemed to stabilise. 


 Figure 11: Death rates from diseases of the heart, 1950-1959

There was an increase in CHD deaths, now reaching 187 per 100,000 per annum, which would be 93,500 deaths per year in a population of 50 million. This should be compared to the 67,200 civilian deaths in the UK and its colonies during the six years of World War Two, so as to appreciate the impact on the population of the epidemic of CHD.


 Figure 12: Death rates from CHD, 1950-1959

1911–1959

In Figure 13 we can see the development of CHD deaths during the years 1911 to 1959. 


 Figure 13: Death rates from diseases of the heart, 1911–1959

The increase in CHD deaths might to a certain extent be the result of improving diagnostic accuracy, but the matching increase in total heart deaths suggests a real change and the development of an epidemic.

On the other hand, the reduction in overall population mortality rate was due to a major decline in deaths from infectious diseases, mainly in children. This has meant an increase in the number of adults who would be at risk of dying from CHD, even though it was obviously new.

To quote from Campbell:

“When we turn to the death rate from diseases of the coronary arteries [CHD] the increase is …. nearly 7,000% above the low level that was recorded in 1891–1920. From this level the death rate had doubled by 1927, doubled again by 1929, again by 1933, again by 1939, again by 1946, and again for a sixth time by 1956.”

In his second paper Campbell expresses the view that the increase of heart and CHD deaths was the result of an ageing population. The major reduction of deaths from infectious disease in childhood (measles and gastro-enteritis in particular) meant that there were more adults, a greater proportion of the population. They would be at risk from CHD deaths whereas children were not. 

However in retrospect this explanation of the onset of the CHD epidemic cannot be true. In the early 21st century we have a population that is ageing very rapidly, especially those above the age of 90 or even 100 years, at a time when the epidemic of CHD has almost come to an end. 

The ageing of the population in the first half of the 20th century was mainly due to the decline of childhood infectious diseases. The ageing of the population in the past 40 years has been the result of the decline of CHD deaths.

1959–1970

Campbell’s study ended with data from the Statistical Review for 1959. He felt that a plateau of heart deaths, and specifically CHD deaths, had probably been reached.

However this was not to be. Death rates continued to increase, and rather than reaching a plateau of stability and constancy, CHD death rates in the UK reached a peak in about 1970, 550 per 100,000 per year. The total number of deaths from CHD would therefore be  about 302,500 per year, more than a third of total deaths. 

In the USA the maximum death rate from CHD was 700 per 100,000 per years, and in Scottish men an astounding 960.

After 1970 the death rate from CHD went into a steep decline. By 1990 (when statins were introduced) the death rate for men was down to 90 per 100,000 per year, and only 30 for women. This was a return to the death rate in 1948. The decline of the epidemic has been described in a previous post.


Figure 14: The epidemic of CHD

**********************

We have clearly witnessed in the “western” industrialised world an epidemic of CHD which was responsible for about 10 million deaths in the UK alone. This epidemic is now almost at an end. It was one of the most serious epidemics in recorded history. It was responsible for far more deaths than the notorious influenza epidemic of 1918 (228,000 deaths in the UK), but spread over a longer period of time and therefore with a less dramatic impact.



References:
Silverman ME. Dr Maurice Campbell. Heart 2003; 89: 1379–1381.
Campbell M. Death rate from diseases of the heart: 1876 to 1959. British Medical Journal 1963: August 31st.p 528.
Campbell M. The main cause of increased death rate from diseases of the heart: 1920 to 1959. British Medical Journal 1963: September 21st. page 712.
Osler W. Principles and Practice of Medicine”. Appleton Press, London 1912: p836.

Coombs CF, Hadfield G. Ischaemic necrosis of the cardiac wall. The Lancet 1926; January 2nd, page 14.  http://dx.doi.org/10.1016/S0140-6736(01)15858-7

Gibson AG. The Lancet 1925; December 19th p 1270.