Friday, 23 September 2016

Coronary Heart Disease – yesterday, today and tomorrow

Coronary Heart Disease –  yesterday, today and tomorrow



I have previously described the major epidemic of coronary heart disease (CHD). Strictly speaking it was a pandemic as it was international, occurring in all continents simultaneously. It has been described clearly in the UK and in the USA. There is good similar data appearing from Canada. 

The data have been based on recorded death rates. The reason is that death is very distinct and a very definite end-point to life. In respect of CHD it is preceded by a well-defined clinical picture of sudden collapse followed rapidly by death, perhaps with severe constricting chest pain. Deaths from CHD have been quite clearly defined, with probably little diagnostic error.

Patterns of CHD

CHD is fundamentally a pathological process that develops insidiously, without the knowledge of the “sufferer”, until a clinical event occurs after a latent interval of perhaps several decades. The disease is one of atherosclerosis, a low-grade inflammatory process with consequent obstruction of the coronary arteries, found on the surface of the heart. It is actually a bit more than atherosclerosis. CHD is usually patchy within the coronary arteries, with "plaques" that are unstable with possible surface ulceration. It is on the surface of these ulcerations that blood clotting (thrombosis) can occur, with sudden complete occasional of a coronary artery.


Figure 1: The right and left coronary arteries and their branches

There are five forms of clinical events:
  • sudden death – the result of myocardial infarction (MI), due to complete occlusion of one of the coronary arteries, which supply blood to the heart muscle;
  • typical MI – severe constricting chest pain with characteristic ECG changes and rise in blood levels of muscle enzymes;
  • left ventricular failure – a result of myocardial infarction, causing serious impairment of function of the left ventricle, with life-threatening accumulation of fluid in the lungs;
  • angina –  the result of incomplete but serious (>80%) obstruction of a coronary artery, with chest pain occurring on exercise;
  • congestive heart failure – narrowing of coronary arteries over a long period of time, without chest pain but reducing blood flow to the heart muscle, as a result of which the heart does not function adequately and swelling of the legs occurs. 


Figure 2: Atheromatous disease of the coronary arteries
Incidence and prevalence

When we are investigating death, or sudden onset of an illness, we measure incidence. This is the number of deaths (or new cases) occurring in a given population size each year, or other unit of time. The incidence of deaths from CHD (death rate) in England and Wales in 1970 was more than 500 per 100,000 population per year. These would almost all have been deaths from myocardial infarction. (MI)

The incidence of (MI), fatal or non-fatal, can also be calculated, as the number of new cases (events) occurring per 100,00 population each year. This is usually obtained from hospital statistics which are reasonably reliable. One of the successes of the UK NHS with its centralised bureaucracy is its ability to collect comprehensive national statistics. But not all people who develop MI are admitted to hospital and admission rates might vary between localities or countries. 

A further and serious problem is that the diagnostic criteria of MI have changed in recent years. ECG changes used to be an integral part of the diagnosis of MI, and I spent many hours learning about ECG interpretation. But now it is stated that the ECG shows no abnormality or no change in up to 75% of cases diagnosed as MI (called NSTEMI – Non ST Elevation MI). It has been necessary to develop a new test of “highly sensitive troponin” so as to identify such very minor and not dangerous episodes of MI, which in the recent past would not have been identified. In the past the frequent diagnosis of "Chest pain ?cause" had an excellent prognosis. This means that during the past ten years it has not been reliable to look at the incidence of MI  because of such a major change in diagnostic criteria.

When we try to identify the presence of an underlying disease that might not have symptoms, there is no clear and recognisable event at the onset. This would apply to diabetes and hypertension, as well as CHD before clinical features have emerged. We can take a “snap-shot” of a fairly small sample (but the bigger the better) of the population and determine how many people have the condition at any one time. This is the prevalence.

Disease mongering

Defining diabetes and hypertension is a difficult process as there are no clear cut-off points between the “normal” population and those who are considered to have the “illness”. The concept of illness implies that the “sufferer” is at a biological disadvantage in respect of early death or disability. 

During recent years the diagnostic thresholds of many conditions (MI, diabetes, hypertension, kidney failure) have been reduced so that by definition more people have the "illnesses" and fewer people remain “normal”. This has been been called “disease-mongering”, expanding the range of a disease and thereby creating “ill” people out of the normal population. This is of very important commercial advantage in many countries to doctors and other health care providers, and also to pharmaceutical companies. There is significant cost to those who pay, but from the viewpoint of the providers this is someone else’s problem, and of course it is "in the best interests of the general population"!

“Monger” is an old English term for someone who creates or sells things, such as an iron-monger or a fish-monger. It is also used in the expression “war-monger”, someone who creates wars. Disease-monger is thus someone who creates disease by simple definition. 

A good example is the new “disease” of female sexual dysfunction, created by medical “experts”. The introductory conference was funded by the pharmaceutical company that was developing the “treatment”. Pre-diabetes, pre-hypertension, and even “high cholesterol” are also non-diseases. They create significant detrimental effects on the innocent “sufferers”, increased insurance premiums, increased medical assessments and pharmaceutical interventions, unnecessary dietary restrictions, and of course great anxiety. These activities give no benefit to the great majority.

Identification of sub-clinical CHD

With many conditions the process of testing is easy – a blood test for diabetes or kidney failure, blood pressure check for hypertension. When it comes to the recognition of sub-clinical CHD the process is more difficult. 

Ideally coronary angiograms are necessary for the identification of CHD, being highly specific (very few false positives – when the test is positive it is strong confirmation of the presence of disease) and also sensitive (very few false negatives – if negative the disease can be confidently excluded). But coronary angiograms are invasive, potentially but only rarely dangerous, expensive, and not acceptable as a means of case-finding. It is only when clinical disease has occurred that coronary angiograms are performed. 


Figure 3: Coronary angiogram

CHD is based on an inflammatory process within the coronary arteries, and  as with chronic inflammation anywhere in the body, after many years there can be deposition of calcium in the inflamed tissues. The calcification can be identified on a CT scan and this can be used as a method of detection of CHD. However CT scanning is also an expensive procedure and it gives a high level of radiation. It is therefore not applicable for population screening, especially as the detection of calcium in an asymptomatic person would not lead to any useful intervention. It might result in higher insurance premiums.


Figure 4: Transverse thoracic CT image of the heart showing calcification of coronary artery

Finally, autopsy studies can be used to identify CHD and assess its frequency (prevalence) within the population. This is not very useful at present as many fewer people die young and autopsy rates have diminished considerably.

Early features of atherosclerosis

Those who do die young and on whom autopsy rates are high are soldiers. It was noted during the Korean War (1950–1953) that autopsies performed on soldiers killed in conflict (and also young  civilians killed in road accidents) frequently showed atherosclerotic change, the precursor of CHD. This led to the realisation that the disease commenced as early as childhood. It appeared that there were several decades between the onset of the disease process and the occurrence of clinical illness. 

During the war in Korea, (1951–55) almost 80% of young soldiers killed in action were shown at autospy to have evidence of CHD, and almost 20% to have it in a severe form. This in itself is remarkable, and it was evidence of the long latent period between pathological evidence of asymptomatic disease and its clinical expression in future years.


In both rheumatic heart disease and syphilitic heart disease there also is a long interval between the onset of the disease process (an infection) and the onset of the clinical illness. It has been possible to assess the prevalence of both as the conditions could be diagnosed by clinical examination. Auscultation of the heart would lead to the identification of damaged heart valves, characteristic of both rheumatic and syphilitic heart diseases, and a blood test (Wassermann reaction – WR) has long been very useful in the recognition of the late effects of syphilis.


We have seen in previous posts details of the epidemic nature of deaths from CHD (= MI). Evidence from US soldiers killed in action are available not just from the Korean War, but also from the Vietnam War  (1968–1975) and the Iraq War (2003). The results show a major reduction in the prevalence of atherosclerosis and CHD during the time of these three wars, from 1968 until very recently. 

The important thing is that early evidence of CHD had become quite uncommon (less than 10%) by the early 21st century. The soldiers killed would have been born during the 1980s, a time when exposure to the causative micro-organism had almost passed and when herd immunity within the population was high.
Figure 5: CHD and severe disease found at autopsy in US servicemen killed in action.


Such data are not available from early stages of the epidemic, from the First and Second World Wars. During WW1 the clinical epidemic had not started and in WW2 there was no major interest in CHD as it was not at the time appreciated as being an epidemic or a major public health problem. 


One thing is clear that in the early years of the 20th century pathologists conducting autopsies were not aware of a significant prevalence of CHD. It was clearly not a significant cause of fatal disease.  But there is historical evidence of atherosclerosis, the pathological process that underlies CHD.

Atherosclerosis in history

Egyptian mummies, about 3,500 years old, have been shown to have evidence of atherosclerosis. One was the Pharaoh Merenptah, who died in the year 1203 BCE.


Figure 6: Egyptian mummy case (Louvre, Lens)

Soft tissues of the unpreserved body do not survive, and there is serious loss of detail even in mummified bodies. However in chronic inflammatory diseases there is often deposition of calcium in the diseased tissues, and this will remain in mummified bodies. The calcium deposits can be detected by X-ray techniques, especially CT scanning. Although not in general use as a method of screening, it has been used in the scientific investigation of mummies. This has resulted in the detection of arterial disease in Egypt 3,500 years ago.

Figure 7: CT scan to be performed on a mummy

The investigators were of course experts in Egyptology and no doubt had only very basic knowledge of CHD. They speculated that these important Egyptians whose bodies were preserved for posterity must have had “atherogenic diets”. Of course we now know that CHD is not a dietary disease and that an "atherogenic diet" is just a popular myth.

But what does the finding from the mummies mean? Was there an epidemic of CHD in Egypt 3,500 years ago? This is possible but it cannot be concluded from a sample of just a few mummies, especially as the hearts had been removed at death and were not available for examination. 

Have atherosclerosis and CHD been present continuously since that time? There is no way of knowing as there are insufficient bodies from the past with preserved soft tissues that can be investigated. 

It is distinctly possible that low-grade atherosclerosis has been present in some individuals during many centuries, in a way that has not had a significant clinical impact. "Hardening of the arteries" has been viewed as a degenerative condition. This might be reasonably correct when applied to the very elderly, but the epidemic of CHD was most certainly not degenerative.


Figure 8: CT reconstruction of remaining internal tissues of an Egyptian mummy

Atherosclerosis and the inflammatory process

We have seen the prevalence of atherosclerosis in young US soldiers killed in action, that it was high in the years of the CHD epidemic, but very much lower in more recent times. It is the persistence in a mild form that suggests that although there might be a background of low-grade atherosclerotic disease, the epidemic of CHD during the 20th century was something different and something special. 

A previous Post has explained that the only sustainable cause of CHD must be a micro-organism. But why one? Is is possible that several micro-organisms can cause arterial inflammation and the development of atherosclerosis? This is suggested as the “dirty chicken hypothesis”, that several micro-organisms might be causative. 


Figure 9: Chickens, probably taking antibiotics

The suggestion is that especially in poor people, who have the highest incidence of CHD death, a number of childhood illnesses create an illness burden that suppresses growth. This can be viewed as similar with chickens and other domesticated animals. Growth of these animals destined for human consumption can be stimulated in a very significant way by giving them large amounts of "routine" antibiotics, presumably supressing low-grade infections. 

It is suggested that in humankind, the inflammatory burden leads to atherosclerosis and CHD. Although a large number of micro-organisms might and probably do cause low-grade atherosclerosis, this is not the same as causing a world-wide pandemic that became the most important cause of death during the 20th century. This would require a very specific micro-organism.

It is well-known that micro-organisms are continuously present in the blood (bacteraemia). Although they are not visible on microscopy or even on culture, they can now be recognised (but not yet clearly identified) by DNA testing. The micro-organisms must have invaded initial body defences - the skin, the respiratory tract, the gums, and the intestinal tract – in order to enter the blood. 

The body has a secondary line of defence processes in the tissues. Bacteria in the blood can invade the walls of the arteries through tiny blood vessels called vasa vasorum, the “vessels of the vessels”. This is well established as the way in which syphilis causes vascular disease, “syphilitic aortitis”. It could and almost certainly will occur with a variety of micro-organisms, but the invasion is halted by immune mechanisms in the arterial wall. 

The immune reaction involves inflammation, a defensive process that is within the experience of all of us. This will ideally eradicate the microbial invasion. If the process is incomplete then it will contain the invasion with continuing low-grade inflammation. The initial part of the defence process is low density lipoprotein (LDL-cholesterol), which is known to have important antibacterial effects. 

The inflammatory process is traditionally characterised by "calor, dolor, rubor, tumor", meaning high temperature, pain, redness, swelling. Although these features are obvious when inflammation is in the skin, they might not always be obvious when in internal tissues. The important feature  of inflammation in the coronary arteries is "tumor", the swelling that is recognised as a "plaque". It is rich in cholesterol as cholesterol is an integral part of the gradual inflammatory process. The greater the expression of cholesterol by an individual, the greater the swelling, and thus the degree of stenosis, narrowing, of the coronary artery. This is what happens with familial hypercholesterolaemia.

Low-grade inflammation of some arteries is likely to be common, just part of life in the elderly and only rarely causing clinical problems. However  if the immune processes are defective, or more importantly if a highly virulent micro-organism is encountered, the defence mechanisms will be overwhelmed, with clinical effects at a younger age. 

Although a background of low-grade atherosclerosis might have been due to a variety of micro-organisms, the epidemic of CHD deaths in the 20th century was clearly due to a new and highly virulent micro-organism. Deaths have been much more likely when immunity has been sub-optimal. The micro-organism concerned has not yet been identified with confidence, but there has not been a major effort to do so. 

The 21st century

What is likely to happen in the future? The epidemic is virtually at an end and we are already in the future. The situation now is that CHD continues but in a very much milder form than previously, and in much older people. There are episodes of MI and these can be fatal, but almost entirely in the very elderly. The great majority of events are not dangerous and there is no abnormality on the  ECG. They would not have been recognised a few years ago, before the re-definition of MI and the introduction of very highly sensitive blood tests.

It is likely that the pattern of CHD deaths has been a cohort effect. People alive between an indeterminate year early in the 20th century and about 1970 would have been exposed to the causative micro-organism, and they started dying from CHD/MI in 1924. The lead time for CHD, what might be called the latent or incubation period, can be several decades. 

We have no idea what this latent period was at the onset of the epidemic, as the acquisition of the micro-organism did not appear to be associated with a clear illness. The initial infections of syphilis (genital sore) and rheumatic fever  (sore throat and joint pains) were usually obvious, followed by a long latent interval before the recognition of heart disease. The latent interval between the acquisition of the causative micro-organism and the development of CHD could initially have been just a few years, with initial exposure immediately after World War One. 

The 1918 influenza epidemic

Could the causative organism possibly have been the one which caused the 1918 influenza pandemic (Spanish flu)? This caused between 20 million and 50 million rapid deaths in the 500 million people affected. As a later effect after a latent interval it is thought to have been responsible for a subsequent 5 million cases of Encephalitis Lethargica, a very serious sleeping sickness (a disease of the brain).

The peak of the epidemic was reached in 1970. If the peak age at death was 70 years, then those dying in 1970 would have been born in 1900. We know from Korean war deaths that the disease process was established in early adult life. Remember that cigarette smoking brings forward death from CHD by 10 years. My father and mother (non-smokers) had both led extremely healthy lives but died as the result of CHD/MI in 1994 and 1997. They were born in 1910 and 1913 and so the time sequence fits into this pattern.

CHD / MI is now a different disease from what we experienced in the years around 1970. It now has a very much lower mortality rate than twenty years ago. This is clear from USA data, in Figure 10. Remember that there were very few effective treatment opportunities between 1970 and 1990.


Figure 10: Mortality rates following MI (USA)
It now affects an older age-group, but as mentioned, this is likely to be a cohort effect. Most of those dying now could have acquired the initial infection in the 1920s or 1930s. They are now the frail very elderly, who have little physiological reserve, and are at risk of death from any minor illness. The main cause of death would be "old age" but there is reluctance for this to be put on a death certificate.

Figures 11 and 12 show a dramatic change in age at death since the peak of CHD deaths, comparing 1968 with 2010. It is much more obvious in men (Figure 11) than women (Figure 12), as CHD death rates were much higher in men.
Figure 11: Shifting age pattern deaths from CHD (UK, men)


Figure 12: Shifting age pattern deaths from CHD (UK, women)
The dramatic clinical features of MI with a very obvious diagnosis, high complication rate and high early death rate (such as I described was the scene in 1970) are now seen only very rarely. Treatment is better today, but as shown in the long-term international MONICA study, the much reduced death rate from CHD is much more due to a reduced incidence rate of events rather improved survival from them. 

Access to coronary angiography and stent insertion was very restricted in the final years of the 20th century. This has changed in the 21st century and availability of the service is now excellent. Although it would have been wonderful had it been available in 1970, it is of much less therapeutic value today. Minor degrees of coronary artery atheroma are readily identified, but the problem is whether these are of an clinical importance. The 20% narrowing of a coronary artery will not lead to any reduction of blood flow. If discovered in a 70 year-old, it can be expected to progress very little during the remainder of life.

There is now concern that too many stents are being placed in very low risk individuals for no clinical benefit. This is of particular concern in countries in which the cardiologist is paid for each procedure. It is of less financial concern with a salaried service as in the UK. However it all is part of the over-medicalisation of society. Doctors generally do what they have been trained to do,(encouraged by the medical manufacturing industry), and so a cardiologist highly skilled in placing stents will place stents, even though the indications were not as strong as in the past.

The question of immunity

There has been an epidemic / pandemic of deaths from CHD during the 20th century. The decline since 1970 has been a combination of decline of deaths, a much-reduced frequency of events, the change to a much milder form of the disease, and a much-improved survival following an event. What has brought about these remarkable improvements?

A decline of the cause is the obvious first thought. As discussed in a previous Post, the only possible cause that fits in with the facts is a micro-organism, the precise identification of which is not yet established. We can ignore dietary (chemical) factors, as despite a great deal of media attention, diet shows no consistent relationship to CHD. 

A micro-organism does not “go away”, and trillions of micro-organisms cannot all simultaneously mutate into a less virulent form. The end of an epidemic is brought about by the population developing immunity.  And so it is with CHD. There is now widespread immunity, and hence the epidemic is effectively at an end.

There is great deal of information demonstrating the importance of immunity, or lack it, in CHD, and this will be the subject of a further Posts.



Wednesday, 7 September 2016

Economy with the Truth - a recent review of Myocardial Infarction

Economy with the Truth - a recent review of Myocardial Infarction




There are two types of scientific paper – the publication of original research and the review article.

The review article has great advantages, mainly because it will include commentaries on many original research papers so that the casual reader will be saved the trouble of finding and reading them all for himself or herself. It is not always easy to locate original research papers unless all regular journals are read, and this must be challenging for those who have a busy work schedule. A way around this is for a department to have a Journal Meeting at regular intervals. Each member of the department will be given a list of a few journals to read, and then interesting articles or extracts will be presented at the meeting. The burden of wide-spread reading is thus shared.

For the individual curious person, such as myself, the review article has another function, in addition to the provision of an opinion. It gives an important way of identifying the large number of papers on a particular topic, so allowing the original papers to be located and read. These will be the papers of original research, and this is the way in which the truth might be encountered.

The search for the truth can otherwise be difficult. There are many vested interests which result in prejudice, and the author of a review article is likely to have a particular viewpoint. It is thus likely that there will be “spin”. This is a political term, implying a corruption of information in the process of turning bad news into good news. There is obviously the opportunity of quoting data selectively, thus depriving the reader from the truth.

It might be thought that I have a viewpoint that I emphasise, and there is some truth in this. My objective is to bring to attention truths that have been hidden or corrupted. This in itself is going to alter the way in which people might view medical issues. My most important objective is to bring to attention the fact that coronary heart disease (CHD) presented as a major epidemic in the 20th century, as so much understanding depends on recognising this.

It is important to remember that the epidemic of CHD in the UK has in reality been an international pandemic, with many millions of premature deaths. The decline of deaths between 1980 and 2007 in several countries is shown in the figure below:


Decline of CHD deaths in men, 1980–2007


I came across the following important and very recent review article in The Lancet. It provides an example of how it is easy to be “economical with the truth” (a famous UK political quotation) and thus “protect” the medical and general public from the reality of the undoubted epidemic of CHD.

…………………………………………………….

Grant W Reed, Jeffrey E Rossi (Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA), Christopher P Cannon (Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Executive Director Cardiometabolic Trials, Harvard Clinical Research Institute, Boston, MA, USA)

www.thelancet.com Published online August 5, 2016

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30677-8/abstract
          …………………………………………………….
This is a full up-to-date and excellent  review of the treatment of myocardial infarction (MI). The term “acute” is not strictly relevant. It implies sudden onset but this is always the case in MI and there is no such thing as the antithesis “chronic myocardial infarction”. The inclusion of the word “acute” is presumably to emphasis the immediate treatment, the main purpose of the review, but that is what can only be expected.
There is mention of a major improvement in the outcome of CHD, which is what we have seen with the rapid decline of the epidemic:
…. substantial improvements in prognosis over the past decade. The progress is a result of several major trends, including improvements in risk stratification, more widespread use of an invasive strategy, implementation of care delivery systems prioritising immediate revascularisation through percutaneous coronary intervention (or fibrinolysis), advances in antiplatelet agents and anticoagulants, and greater use of secondary prevention strategies such as statins. 
“….the past decade….” gives an inappropriate time-frame. The improvement in prognosis has been happening for much a longer time. Medicine did not begin in the 21st century.
The review makes no acknowledgement that MI (coronary event) has become much less frequent, as has been identified by the international MONICA study (multinational monitoring of trends and determinants in cardiovascular disease) and other international statistics. It emphasises the importance of medical interventions, the importance of which is regarded in the MONICA study of being of less importance than the reduction of events.
Under the heading of “Epidemiology” the paper stated:
MI …. causes more than 2·4 million deaths in the USA, more than 4 million deaths in Europe and northern Asia, and more than a third of deaths in developed nations annually. 
This is not not very meaningful because, as we have seen, the number of deaths has decreased substantially (by about 95%) during the past 45 years. The authors are clearly not epidemiologists. It is as though CHD and its most important manifestation MI has always been with us. There is no attempt to indicate the epidemic nature of the condition.
It goes to state that:
Since the mid-1990s there has been ….  an overall decline in myocardial infarction.
But why only since 1990? This is the time that effective treatments were first introduced on a wide scale. The authors could have stated that between 1970 and 1990 there was an 85% reduction in the age-adjusted death-rate from CHD (effectively from MI), and that this must have been spontaneous as effective treatments were not available. This omission was spin, as this well-reported fact did not fit into the theme of effective treatments.
Although the authors do not state clearly that the nature of MI has changed and that it has become a much milder disease during recent decades, they make the comment:
Since the mid-1990s there has been a steady decline in the proportion of patients with ST-segment elevation myocardial infarction (STEMI), and a smaller increase in non-STEMI (NSTEMI), leading to an overall decline in myocardial infarction. Today, NSTEMI comprises 60−75% of all myocardial infarctions 
The STEMI is an episode of MI in which the ECG shows an abnormality with elevation of the ST segment (see previous post on simple ECG interpretation). The NSTEMI is an episode of MI in which the ECG is most likely to be normal, or showing no change from a previous recording.
As I have mentioned in a previous Post, at the height of the epidemic in 1970, when the mortality rate from an episode of MI was about 50%, the ECG was of much greater importance. The hallmark of MI was the Q wave, and this indicated full-thickness damage to the heart muscle. With the milder form of the disease the Q wave is effectively confined to history as it is seen so really now. 
The authors also report that:
A combined task force of major professional societies revised the definition of myocardial infarction in 2012.
The redefinition of MI has resulted in the diagnosis becoming much more common. Following an episode of chest pain with a normal ECG, a rise in the blood level of the highly sensitive cardiac troponin would lead to a diagnosis of MI (NSTEMI) today, whereas that would not have been the case ten years ago. These new cases receive the same treatment as the more obvious MIs, thus keeping the interventional cardiologists busier than ever. The prognosis is excellent.


The epidemic of CHD deaths in the UK
So we can see the spin, the economy with the truth, and most importantly another failure to identify the epidemic of CHD, described clearly in the UK and in the USA.
The review gave an excellent account of the treatment options available today.

But remember, during the 20th century CHD / MI was one of the most serious epidemics of all time.














Monday, 18 July 2016

The cause of coronary heart disease

The cause of Coronary Heart Disease

 Illustration: Ben Lamb for the Guardian

Previous posts  have described the undoubted epidemic of coronary heart disease (CHD) in the UK and in the USA, its appearance immediately after 1924 in other than rare case reports, its exponential increase, its peak in 1970 in the UK, and its rapid and exponential decline, 80% by 1990, 95% by 2010.
heart disease history
The emergence of coronary heart disease in the UK


It has been responsible for the premature deaths of ten million people in the UK alone. Its almost complete disappearance has had a major impact on the population profile of the UK, and now twice as many men live beyond the age of 85 years compared with 1968. There is an exponential increase in the centenarians in the UK.

Looking with the cold mind of objectivity and economic idealism, CHD was actually a very convenient epidemic. The disease process itself started in early adult life, with its clinical manifestation appearing between two and five decades later. Most of those who died from CHD were men. Some died during their working lives, but the majority died shortly after the normal age of retirement at 65 years. They therefore contributed fully to the national economy, they paid into pension schemes, and they then died suddenly and therefore cheaply, having taken little out of their pension funds.
age at death males UK
Male deaths, age at death, 1968 and 2010, UK

This might sound callous (I will avoid the description of “heartless”) but it is factual and it explains some of the problems that are appearing now that the epidemic has come to an end.  We are a time without pestilence. More people, and especially men, are living many years longer, and the longer lives can be seen in the figure above. They are expecting pensions to continue at previous rates for perhaps thirty years rather than ten. They (we) are now not just living longer but dying more slowly, and this is putting serious strains on hospital beds, and health and social services in general.


The dramatic decline of deaths from coronary heart disease has increased the average life expectancy, with a large increase in the number of very old people, but it has had an inevitable effect on retirement pensions.


An amusing view of pension arrangements for young people (when they are older)

But what has been the cause of the epidemic? Why did it suddenly emerge? Why did it spontaneously decline to such a major degree, perhaps to disappear completely in the near future?

We need to consider Europe and North America in particular, at the time of the emergence of CHD. Conditions then were described as follows:

The cause of CHD can hardly be viewed as the good life, but despite the depression, life was arguably better in the USA than in Europe.

In general the fundamental causes of disease are few, either determined genetically at the moment of conception, or acquired subsequently. In the present age of science and enlightenment, he broad categories are as follows:

  • genetic
  • psychological
  • physical
  • chemical 
  • biological

There are also congenital abnormalities, which are maldevelopment, a form of injury, that might occur rarely and unpredictably in isolated individuals. There are other forms of injury occurring at various ages. These are not “diseases”, as this would imply a condition that occurs suddenly or which is progressive, with disability or deterioration that shortens life.

In respect of CHD we need to look at these in turn and objectively, without starting out with a conclusion. There has been a lack of objectivity during the past 50 years, since the epidemic was identified. 

We must remember the vital discovery of ignorance and we must avoid jumping to popular conclusions, assuming God or the new god of diet to be the cause of disease.


Genetic factors

There is no question that CHD runs strongly in families, and indeed a strong family history is the most powerful risk factor, far more powerful than cholesterol. But this does not equate to genetic transmission. 

Tuberculosis ran in families equally if not more strongly. It was thought to be “constitutional”, effectively meaning inherited. Perhaps it was, but inheritance was in the form of the causative micro-organism, passed on at some stage after birth. Syphilis was also strongly familial. It could be passed from mother to child across the placenta (congenital syphilis), or between siblings by close rather than by sexual contact.

At the present time a great deal of progress is being made concerning our inheritance of micro-organisms, especially from the mother, which might be trans-placental, during the process of birth, and during the first few years of life.

There are other forms of inheritance other than genes and micro-organisms. They include religion, location of domicile, education, money, housing, perhaps diet. All these have an influence on CHD (through mechanisms that are far from clear) but they cannot be responsible for such an epidemic. These factors might influence susceptibility but they cannot be regarded as the cause.

The familial incidence of CHD is variable but can be very high, much greater than a Mendelian pattern of inheritance. CHD can be present in all family members.

But of the greatest importance is that an epidemic can never be the result of genetic factors. The spread of a new genetic mutation takes many generations, and there were only two generations between the onset of CHD and its peak. The bacterium E coli might have 70 generations per day, allowing rapid evolution of a mutation, but 70 human generations would take 2000 years.

The epidemic of CHD in the UK

Another nail in the coffin of the postulated genetic cause of CHD is the rapid decline after 1970. A genetic mutation can appear, but it can most certainly not disappear in the way of CHD deaths, not as adult deaths.

There is the genetic condition of familial hypercholesterolaemia (FH), in which there is a high level of cholesterol in the blood. This predisposed to early CHD death during the 20th century. However as I have described previously, the genetic abnormality (mutation, polymorphism) was not new, and it is very important to acknowledge this. 

In a well-researched family with FH in the Netherlands, there was a very distinct health and survival advantage during the 19th century, but this was before the epidemic of CHD. During the epidemic of CHD the family members with FH experienced a reversal of fortune and were subject to premature death. This was factor of susceptibility to CHD or increased severity of it. 

FH cannot be regarded as the cause of the onset and decline of the widespread epidemic. Only a tiny (but well-studied) minority of those having and dying from CHD had FH. 

CHD is not and cannot be regarded as a genetic disease.

Psychological factors

The proposal of CHD being caused by psychological factors (never clearly defined) has had strong proponents. Generally “the mind” has been attributed to be the cause of a variety of diseases when ignorance has been the truth. But honest acknowledgement of an absence of knowledge leaves a vacuum to be filled by  variety of wild guesses. 

It was so often assumed that a hard-working business executive who experienced or died from CHD, specifically from myocardial infarction, did so because of the psychological damage resulting from hard work. “He worked himself into an early grave” was often heard. 


When good quality epidemiological studies were undertaken it was clear that those most at risk from early death from CHD (and almost all other causes of death) were the long-term unemployed.

There is simply no evidence that psychological factors cause disease as a pathological process. They can however influence the progression of the illness, an individual illness that is influenced by personal factors. 

In respect of CHD, psychological factors can precipitate acute myocardial infarction (MI) or death, but only in someone who already has advanced disease. These can be called “acute excitable states”. An excellent example occurred on a national scale on June 30th 1998. This was the day in which England played in the quarter-final of the World Football Cup, and lost to Argentina in a penalty shoot-out. 



On studying retrospectively hospital admission statistics, there was found to a 25% excess of admissions to hospital on account of CHD on that day and the following two days.  This is considered to be the result of over-excitement of those with sub-clinical but advanced CHD who were watching the television on that day. Although the psychological factor might have brought forward clinical expression of disease or even death by a few days, psychological factors could not have been responsible for the disease itself.

Furthermore, although mass hysteria might produce a health problem on a given day, psychological factors cannot be considered to be responsible for the rise and fall of an epidemic during the course of almost a century. There is no obvious explanation of a psychological cause or mechanism of either the rise or fall of the epidemic.

Physical factors

There is no question that a natural physical event such as an earthquake can cause a large number of deaths, but these are mainly sudden and they cannot be classified as disease, even though disease can cause deaths as a secondary process. 

Global warming might be responsible for large numbers of deaths in the future, but there will be more specific causes of those deaths. “Global warming” would not be acceptable on a death certificate.




Physical causes of death include extreme cold (hypothermia) or excessive heat (hyperthermia), extreme deprivation of water or food, major trauma or drowning. 

But these are applicable to individuals. Even on a large scale, such as an earthquake or a tsunami, an epidemic is not an appropriate term if there is no disease. Physical factors cannot explain an epidemic that took 45 years to reach its peak and then another 45 years to virtually disappear.

Chemical factors

Chemicals can certainly lead to large numbers of deaths over a long period of time – think of severe atmospheric pollution, reaching its peak in London in about 1953, but still on the increase in many cities of the world. However the actual cause of death was mainly the specific disease of chronic bronchitis. Atmospheric pollution is a serious risk factor for CHD: death rates are greater in inner city areas compared to rural areas, and death rates are lower with residence at high altitudes. Atmospheric pollution was the norm in industrial cities a century before the onset of the epidemic of CHD. Death from CHD can occur in the presence of clean air and “poisoned air” cannot be regarded as the cause of the epidemic.

Cigarette smoking must also be considered as a possible chemical factor causing the epidemic of CHD. Cigarette smoking certainly increased after World War 1 and many fewer people smoke now. However, as explained in a previous Post, cigarette smoking can only be regarded as an accelerating factor of CHD and not its cause. 


In the landmark study of doctors (modern studies are no longer possible), 20% of heavy smokers died from CHD but also 20% of non-smokers. In heavy smokers the deaths occur on average ten years earlier, and at the age of 50 twice as many heavy smokers had died compared to non-smokers. Cigarette smoking cannot be the cause of the epidemic of CHD, but it has been an important co-factor.

Death from chemicals can usually be regarded as poisoning. Is there any chemical that could have fatally poisoned ten million unsuspecting people in the UK between 1924 and the present time? There is only one chemical that has been considered seriously and that is cholesterol.

The cholesterol story is long and confused. To qualify as a poison the dangerous effect of the chemical must increase with the amount ingested and with an increase in its blood level. Conventional wisdom is that these are true, hence the strong advice to minimise the cholesterol content of the diet and also of the blood. There are many reasons to doubt this conventional wisdom, especially from the Framingham study, and also the observations that above the age of 60 years a high blood level of cholesterol gives a very significant survival advantage.

It is not possible to explain the onset of the CHD epidemic on the basis of dietary cholesterol or any other dietary constituent. 


Recommended reading

Without diet the cholesterol story is lost. If allegedly poisonous cholesterol is endogenous (produced from within the body) the implication is that we are dealing with a genetic metabolic condition, but we have eliminated a genetic cause of an epidemic. The human body cannot be expected to synthesise a deadly poison on such a large scale.

Similarly there is no dietary explanation for the sudden and rapid decline of CHD deaths after 1970. The 85% reduction of CHD deaths before the introduction of statins indicates that the rapid decline was not due to medical and public health interventions.

Sugar is also stated to be dangerous to our health. There are great efforts now to reduce population-based sugar intake. This is at a time of exceptional low age-related death rates and increasing survival into very old age. The rise and decline of CHD cannot be attributed to sugar as a poison.

The CHD epidemic cannot be explained on the basis of a chemical factor.

Biological factors

The process of elimination is part of intuitive reasoning, as defined by Sir Karl Popper (1902–1994) and Sir Peter Medawar (1915–1987). Suggestions, hypotheses, are rejected when they do not explain the facts. Scientific reasoning is based on a process of falsification.

We have rejected postulated genetic, psychological, physical and chemical causes of CHD. We now need to reject if possible the suggestion that CHD might be due to a micro-organism. If this is also rejected, we are back to assuming that the epidemic was the will of God!

Microbial diseases can occur in epidemics, starting with the mutation or cross-species transfer of of genetic material in perhaps just a single micro-organism. Rapid cell division (many generations per day) leads to transmission that is exponential with progressive doubling, as is usual in biological systems. A microbial epidemic comes to an end when the population at risk has been reduced or protected, and when the remaining population develops immunity, either natural or by immunisation. 

"Herd immunity” occurs when acquired immunity is passed to the next generations and thereby spreads through the population. It gives partial if not total protection. When international travel exposes a population to a disease previously not encountered, then the lack of herd immunity can have devastating effects. For example, smallpox wiped out a large proportion of the population of the West Indies after the arrival of Europeans.

The body’s response to attack by a micro-organism is defensive inflammation. If the micro-organisms are present in the blood, then the arteries are at immediate risk. LDL-cholesterol as lipoprotein is a first line of defence in the wall of the arteries, followed by the mobilisation of inflammatory cells, neutrophils, T-cells and macrophages. Production of specific antibodies follows as a secondary and lasting defence.

The pathology of CHD is characterised by inflammation, and this is obviously compatible with an infective cause. 

There is no obvious reason to reject the suggestion of a microbial cause of the CHD epidemic.

Precedents - biological models

There are heart diseases other than CHD are known to be caused by micro-organisms. 

Syphilitic heart disease

Syphilis was introduced into Europe by the crew of the ships of Christopher Columbus returning from what was to become known as America. Cardiovascular disease is a late manifestation of syphilis, like dementia (general paralysis of the insane – GPI) and spinal disease (tabes dorsalis – TD), and soft-tissue tumours (gummas). There is a long incubation period of many years between acquisition of the infection (primary lesion, or chancre) and the clinical manifestations of the serious diseases (tertiary syphilis). The cardiovascular diseases resulting from syphilis are aortic aneurysm (especially thoracic aorta) and incompetence of the aortic valve.


Treponema pallidum, the spiral bacterium that causes syphilis

Rheumatic heart disease
This is the result of the bacterium Streptococcus pyogenes. The first phase of the condition is rheumatic fever, which usually occurs in childhood, and which can follow immediately after a throat infection (“Strep throat”). Again there is a latent period of many years before the clinical manifestations of heart disease occur. The form of the heart disease is damage to the heart valves, especially the mitral valve. 


Streptococcus pyogenes, the cause of rheumatic heart disease


Endocarditis
Bacteria from the circulation can colonise heart valves that are either congenitally abnormal or much more commonly damaged as part of rheumatic heart disease. Artificial heart valves can also be colonised as part of the spectrum of endocarditis, also known as subacute bacterial endocarditis (SABE).


Streptococcus viridans, the major cause of endocarditis

Myocarditis
Acute inflammation of the muscle of the heart, the myocardium, can be the result of a presumed or identified viral infection. It might present with palpitations, chest pain, or sudden shortness of breath due to heart failure (which can be fatal). The illness can follow an upper respiratory tract infection that is assumed to be due to a virus. Several viruses have been identified but usually no identification can be made.

Coxsackie B virus, the major cause of myocarditis

Kawasaki disease
This rare condition has only been recognised since the original description in 1967 by Tomisaku Kawasaki. It occurs in young children and the initial feature is high fever with a rash. This suggests a viral cause but a definite causative virus has not so far been identified. The second phase of the illness is a vasculitis with inflammation of the coronary arteries, which can result in myocardial infarction that can be fatal. The pathology of the coronary artery lesions is different from that of CHD, but it is again inflammatory indicating that there are perhaps several coronary artery diseases.

Patterns and proofs

With a biological epidemic we are able to observe a characteristic pattern of a rapid and exponential increase of disease, the reaching of a peak, and then a similar rapid and exponential decline. In an epidemic such as influenza we expect the time-scale to be in weeks, if international the time-scale might be months.

We do not expect epidemics to have a time-scale of years or decades, but there is no reason why not. An acute illness such as a streptococcal throat infection or the primary lesion of syphilis following sexual contact will be obvious, but not the long-term effects appearing after a delay of years or decades. Although syphilis first appeared in Europe in 1493, it was only in 1875 that cardiovascular disease was linked to previous primary syphilis.  There was effectively an epidemic of syphilis and its long-term effects, almost coming to an end in the late 20th century, helped by penicillin and public health measures.

The epidemic of “Spanish” flu immediately after World War 1 was obvious, serious, and international. It is thought to have infected up to 500 million people across the world and was responsible for perhaps 50 million deaths. 



But less well-known was the epidemic of encephalitis lethargica, that occurred slightly later, up to 1926. It affected about five million people. Its cause is mysterious but a strong possibility, indeed an assumption, is that it was a result of the influenza virus affecting the brain. Research opportunities were not available at the time. 
Encephalitis lethargica

The early pathological features of atherosclerosis and CHD can be recognised at autopsy performed on young men who have died as the result of trauma, road accidents and warfare (there has been a major reduction in the frequency and severity of these findings in recent years). It is many years or decades later that the clinical manifestations of sudden death, myocardial infarction, angina, left ventricular failure. The long latent period in the development of CHD is comparable to other heart diseases due to micro-organisms. 

This supports the suggestion that CHD might also be due to a micro-organism. There is nothing to contradict this suggestion. 

In the absence of an alternative viable hypothesis, we must assume that the microbial hypothesis of the causation of CHD is likely to be true.

The micro-organism

I have not indicated a specific micro-organism. The microbial causation of a disease is based on epidemiology and the recognition of a pattern of disease. This is supplemented by a careful study of the compatible pathology of the condition. This will add to plausibility, as would comparisons with other diseases. 

The next stage, to identify if possible the specific micro-organism, would be the work of micro-biologists and other laboratory scientists. Once a putative micro-organism is identified, conclusive experimentation is limited by an ethical and understandable inability to undertake human transmission studies.

We must remember that many microbial diseases have been accepted as having a microbial causation long before the micro-organism were identified. In recent years viral hepatitis was accepted before the various viruses (A,B,C etc) were identified. AIDS was accepted as being due to a virus before HIV was identified.

Absolute proof is not possible. What we want is the best answer, and this is the normal scientific method. It will conform to Hill’s Criteria. If there is no animal model (and that is usually the case with human disease), then Koch’s Postulates cannot be fulfilled.

There have been proposals of a micro-organism that might cause CHD. This will be the subject of a future post.

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