Friday, 8 March 2019

Epidemic and Endemic Coronary Heart Disease

Influenza is always with us and no doubt always has been. It affects a significant number of people each winter and it can cause deaths, especially of the vulnerable very elderly. This is endemic influenza: it is more or less constant within the population (end- means within). But occasionally the population experiences an epidemic of influenza (epi- means without or outside). This affects a large proportion of the population with a much higher death rate than the endemic form. An epidemic of influenza is due to a new, a mutant, strain of the influenza virus to which we have no immunity. However we develop immunity rapidly, and so the epidemic subsides. 

It is the same with coronary heart disease (CHD) and myocardial infarction (MI).

The two major epidemics of the 20th century

Immediately following the end of World War One in 1918 the population of Europe experienced an epidemic of influenza. It became known as “Spanish Flu”, and as it occurred in all continents it can be described as a pandemic. It affected worldwide about 500 million people and it was responsible for the deaths of up to 100 million. 

War cemetery at the beautiful marble Bodelwyddan Church, North Wales.
The graves are of Canadian soldiers who died from influenza
shortly after the end of World War 1

War grave of one of the many Canadian soldiers
The second major epidemic was that of many deaths from CHD. It was a disease the basis of which started at about the same time as the influenza epidemic, but it had a long latent interval before the occurrence of clinical effects and the large number of deaths. 

We have all been aware of the many deaths from CHD that occurred during the 20th century. I have described how this appeared as a new cause of death during the 1920s, rising exponentially to a peak in about 1970. CHD became by far the major cause of death, and it was clearly a well defined epidemic. Indeed, as it occurred in temperate zones in all continents it was an international pandemic. Although CHD deaths were mainly in people over the age of 70 years, there were many deaths in younger people.

The epidemic of CHD in the USA, 1940 to 2000. Data from W Rothstein.

The peak of the epidemic in 1970

1970 was time of medical drama, the peak of the epidemic of severe high-mortality CHD. At this time I was busy as a young doctor working in emergency hospital medicine and I remember it vividly. There were many patients admitted severely ill with obvious myocardial infarction (MI). They had a high death rate: almost half died before they reached the hospital, and 35% of those admitted died in hospital. 

They were found to be very likely to suffer from the new experience of “cardiac arrest”, later identified as the immediate result of ventricular fibrillation (VF). ECG monitoring, cardio-pulmonary resuscitation (CPR) and defibrillation came into existence; coronary care units had to be invented. But this was in 1970, very different from the present time, or even in 1990.

Case fatality rate after admission to hospital due to MI,
peak of the epidemic and during its decline

This was the greatest epidemic of the 20th century, and also a worldwide pandemic. Over a much longer time-span (fifty years rather than weeks), it was responsible for more deaths than Spanish Flu. Short memories and a long time-scale mean that few people appreciate it as an epidemic, but it was.

CHD before the epidemic

It is likely that CHD existed before the emergence of the epidemic in the mid-1920s. Historical evidence is far from complete as soft tissues such as arteries decompose after death – except when the body is embalmed. Examples of this are found in Egyptian mummies, and evidence of atherosclerotic disease has been identified. Atherosclerosis, hardening of the arteries, is the background of CHD, with plaque disruption and rupture being the precipitating event of MI (“heart attack”). In the ancient Egyptian experience, CHD, although present, could not be identified as the cause of death. 

Cross-section of a critically narrowed coronary artery,
obviously having caused death.
CHD as a disease can be present for many years without it ever causing symptoms or illness, or even death.

During the Korean war (1950–53), autopsies performed on young soldiers killed in action established the presence of arteriosclerotic CHD in almost 80%, and severe disease in almost 20%. This was twenty years before the peak of the epidemic. It demonstrates a long lead time, and had they not been killed in military action they would probably have died at the peak of the epidemic twenty years later, some earlier, some later. The disease process of the epidemic was well established before 1950. In fact by the time of the Vietnam war (1968–78) the prevalence of atherosclerotic disease in soldiers killed in action had fallen by half, and by the time of the Iraq and Afghanistan wars it had almost disappeared.

Evidence of asymptomatic CHD in young US soldiers killed in action in successive wars.
The decline of the disease is obvious.

Chest pain ?cause

In the years following 1970 there were many people who presented to emergency services with chest pain suggestive of MI. The great majority were not ill and they survived. The ECG was normal and blood enzyme tests were also normal. There was thus no objective evidence of MI/CHD, or any other active disease process. This was in the era before the extensive use of coronary artery imaging. 

A large sample of this group of patients with what was called “chest pain ?cause” was identified in Nottingham, UK, and reviewed after the lapse of a few years. After one year none of those whose diagnosis was chest pain ?cause had died, compared to 30% of patients with a diagnosis of MI. This excellent outcome of chest pain ?cause was obviously very reassuring.

CHD since the end of the epidemic

The main feature during the epidemic of CHD was the very high death rate, but the clinical scene is very different now. A patient who presents to the hospital emergency department today with chest pain is likely to have a normal ECG

Normal ECG

The “Q wave MI”, common in 1970, is now extremely rare. During the latter years of the epidemic we would see an abnormal ECG with ST segment elevation even if no Q wave, but at present we find an ECG with neither Q wave nor ST elevation . This is the “non-STEMI” (non-ST elevation myocardial infarction). This means a normal ECG, indicating minimal heart damage, a condition that would have been diagnosed as “chest pain ?cause” in 1970, with an excellent prognosis.

Q wave MI, common in 1970, rare today

Changes in the diagnosis of MI

When the heart muscle is damaged, enzymes are released from the cells into the blood, where they can be detected and used as confirmatory evidence of MI. The enzyme tests used in the 1970s are no longer in use because they lack “sensitivity”. This means that it was possible that some people in the “chest pain ?cause” group had actually experienced a very “mild” MI without it being recognised, ECG and enzyme tests of the day being normal. 

The next development was a new blood test of “troponin”, again detecting chemicals released from damaged heart muscle cells. This was a more sensitive test: it was positive in cases when the ECG was normal and when the older enzyme tests would be normal. This means that more people with “chest pain” would be diagnosed with MI.

And then in the early 21st century, there was the development of the high-sensitivity troponin test, so that even more people with chest pain would be diagnosed with MI. In previous years this diagnosis was not possible: the patient would have discharged with a label of “Chest pain ?cause”, knowing that there was a good outlook and no cause for concern.

Evaluation has shown that there is no need for concern in people diagnosed as “MI” the basis of only elevated high-sensitivity troponin. It creates more “patients” (patient mongering), with no benefit to themselves, but probably much more anxiety, and of course more activity and income for doctors and other health professionals. 

Coronary angiography

In the 1970s coronary angiography was something very new and not available on a wide scale. Today it is a readily available investigation and the number of angiograms has increased dramatically. The purpose is to identify the condition of the coronary arteries (the arteries that supply blood to the heart muscle). 

Diagrammatic representation of the coronary arteries,
showing the presence of disease and narrowing.

At present about 250,000 coronary angiograms are performed each year in the UK. The purpose of the investigation is not to diagnose MI but to assess the degree of coronary artery disease, and a measure of narrowing of coronary arteries. Following angiography, stent insertion is performed if necessary, about 100,000 per year in the UK.

In respect of patients with MI diagnosed in the traditional way, we expect to see critical coronary artery narrowing, perhaps an 80% or greater narrowing. Under this circumstance the insertion of coronary artery stents would be important, the purpose being to prevent further episodes of MI and possible sudden death. 

It is unfortunate that widespread coronary artery stent insertion was not readily available during the epidemic of CHD. Now that it is readily available we find that the epidemic of severe and high-mortality CHD has come to an end. We are in an era of endemic CHD, a disease that might have been with us since antiquity, and which is in a mild form with a low mortality rate. Most MIs would not have been identified in the past, but now they are. 

A diagnosis of MI is followed as soon as possible by coronary angiography, but today coronary artery disease is much milder and severe stenosis is much less common. Nevertheless coronary artery stents are used more than ever, and this has led to criticism concerning overuse of stents when risk of death is low.

The cause of endemic  CHD

Few people seem to be aware that CHD has undergone a major change since the peak of deaths in 1970, mainly because those, like me, who were at the front end in 1970 are no longer in clinical practice. Personal experience forms opinions. But what has happened: what is the reason for this change?

I have expressed previously thoughts on the causation of CHD . First, an epidemic cannot be genetic, and its development is the result of external factors. These could be chemical or biological. Chemicals from cigarette smoke appear to be accelerating rather than the prime mover of CHD. Chemicals in the diet (mainly cholesterol) have been assumed to be the cause, but confirmatory evidence is far from clear: it must be concluded that CHD is not a dietary disease. It has only recently that CHD has been accepted as being an inflammatory disease, and it is most likely that inflammation is driven by infection.

The infection is the result of micro-organisms circulating within the blood stream, a common or even “normal” event, a low-grade bacteraemia. Bacteria can enter the walls of the arteries through the vasa vasorum (the blood vessels of the blood vessels). 

Diagram of the wall of an artery.
The vasa vasorum provide a blood supply to the wall of the artery, in particular to the media, the muscular part of the artery. It is here that the disease process of atherosclerosis begins, NOT from deposition of cholesterol from the blood on to the internal surface of the artery (the intima)

Body defence mechanisms then come into play, so as to control and neutralise the bacterial invasion. The first line of defence is LDL-cholesterol. Although this leads to the accumulation of cholesterol in the artery wall, its purpose is defensive. If the micro-organism is recognised by immune memory, elimination of a bacterium is aided by the mobilisation of immune mechanisms,.

Bacteraemia is common, the result of a wide variety of micro-organisms, some known and some (probably most) not yet identified. It is inevitable that during life we will encounter a large number of bacterial invasions of our arteries, more if our immunity is impaired. As a result we will accumulate the low-grade inflammatory process that becomes atherosclerosis. This might ultimately lead to low-grade endemic CHD.

The cause of the epidemic of CHD

But a high virulence organism might appear, a novel micro-organism to which there is no innate immunity, and this would cause an epidemic. An epidemic arises with the appearance of a new micro-organism, and it later subsides because of the development of immunity, which will be inherited to protect future generations.

When syphilis first came to Europe in the early 16th century, it caused a sexually transmitted disease that appears to have been much more severe than it was 400 years later. It became a long-term epidemic that was often disabling and fatal, as the result of its later neurological and cardiovascular disease processes. Syphilis is due to the bacterium Treponema pallidum, and it was the cause of an epidemic of heart disease which came to an end at about the same time as the emergence of the epidemic of CHD.

Treponema pallidum, a spirochaete,
the cause of syphilis, that can cause serious and fatal heart and arterial disease

Rheumatic fever in Europe became almost extinct during the 20th century. Its origin is far from clear, but its decline was probably spontaneous, helped (as with syphilis) by susceptibility of the causative micro-organism to penicillin. It was another microbial cause of serious and fatal heart disease, due to the bacterium Streptococcus pyogenes.

Streptococcus pyogenes, strings of spherical bacteria (cocci).
The cause of rheumatic heart disease.
The long-term endemic form of CHD is due to a variety of low-pathogenicity bacteria, but the epidemic must have been due to just one micro-organism, almost certainly Chlamydia pneumoniae, or a specific mutant of it.

Chlamydia pneumonia, a tiny and ancient bacterium
that can only survive within the cells of a host.

Chlamydia pneumoniae is usually but not always detected in CHD. Although it is likely to have been the cause of the epidemic of high-mortality CHD, the endemic disease due to a variety of other micro-organisms continued during and after the epidemic. 

Review of the Chlamydia pneumoniae story will follow in a future Blog post.