Saturday, 30 January 2016

The 20th century CHD epidemic - report from the USA



Tucson, Arizona

Several of my Posts refer to the epidemic of coronary heart disease (CHD) that occurred in the 20th century, and which is now almost over. I reported this in the medical literature (Quarterly Journal of Medicine) in 2012.

People may question my assertion that there has been an epidemic of CHD, but as I have mentioned previously the evidence is well documented. The national documentation requires a level of organisation which is not always present but it is present in the highly sophisticated civil service of the UK and the documents are readily available. The national registration of deaths has been present since the late 19th century, and the great advantage of the NHS is that vast quantities of data have been created and saved.

I have just come across a publication from a medical team from the University of Arizona School of Medicine, concerning “The 20th century epidemic of CHD”. It was published in 2014 in the American Journal of Medicine. The study is based on exclusive USA data and no reference is made to my earlier work, which used mainly UK data.

It mentions that “heart disease” was only the fourth common cause of death in the USA in the early years of the 20th century, but by the middle of the century it had become the most common cause. It did not identify rheumatic and syphilitic heart disease which were present in the early years, but they were declining as causes of death. The deaths from these causes would have reduced to zero by 1970. Something new was appearing to increase substantially the total number of deaths from heart disease.

Working in Chicago, Dr James Bryan Herrick (1861-1954) was in 1912 the first to diagnose myocardial infarction (MI), the most serious and important manifestation of CHD. This is a sudden episode of severe chest pain with collapse and high risk of early death, loosely called a “heart attack”. The clinical diagnosis was straight-forward but it required pathological corroboration from autopsy evidence to understand the condition. A few years later Herrick was one of the first to use the electrocardiogram (ECG) as an aid to diagnosis of MI. Herrick was also the first to identify Sickle Cell Disease, initially called Herrick’s Disease.

But the diagnosis did not just depend on clinical features and ECG. The condition had a high mortality rate. Pathology was of supreme importance and the autopsy was a vital way to learn.  At the time imaging procedures were effectively unknown, X-ray machines identifying only major damage to bones. 

The correlation between clinical features and findings at autopsy (clinico-pathological correlation) was a major part of medicine until very recently. Whereas in the earlier years of the 20th century the ward round would end in the autopsy room, in later years it would end in the X-ray imaging department. Continuous learning is integral to clinical medicine and looking inside the body is part of this.

And so the pathology of MI, and CHD in general, became well established during early part of the 20th century. The emergence of CHD, the new epidemic, was clear and beyond dispute. There were those who wondered how they could have missed the diagnosis in the years before the First World War, but although they did not fully understand this, the disease was simply not present at that time.

Figure 1. Decline of deaths from CHD in the USA

The emergence of a new disease was certainly a mystery, but during the first half of the 20th century there were more important events in the USA and Europe, such as two world wars and a catastrophic economic depression between them. As Dalen and colleagues point out, it was the subsequent sudden decline in deaths from CHD in the late 1960s, clear from good quality national data, that caused surprise.

rise and fall of CHD
Figure 2 The rise and fall of deaths from heart disease in the USA

The data is not entirely clear. Figure 1 shows deaths from CHD per 100,000. I assume that the data are age adjusted but this is not stated. Similar for Figure 2, but this shows all heart deaths and not just CHD. There is no data given for specific CHD deaths before the 1965 peak but the increase in total heart deaths was clearly due to the emergence of the new CHD.

The peak of CHD deaths is identified as 466 per 100,000 per year, slightly lower than 522 in the UK. The peak in the west of Scotland was an astounding 960 deaths per 100,000 men per year. The decline of heart disease deaths in the USA appears to be only to 130 per 100,000 per years, but this is total deaths. Although the overall decline is the result of many fewer CHD deaths, in the UK the CHD deaths had declined to only 40 per 100,000 per year (age adjusted) in 2007.

Dalen and colleagues also report autopsy findings in US soldiers killed in wars. In the young men who died in the Korean war (1951–1953),  pathological evidence of CHD was found in 77%. This had fallen to 45% in those who died in the Vietnam war (1968–1978), and to 8.5% in those who died in the Iraq and Afghanistan wars (2000–2011). There is clearly a major decrease of the pathological basis of CHD, corresponding to the decrease of deaths in the general population.

decline of CHD
Figure 3: CHD findings at autopsy in young US soldiers killed in wars

The clinical consequences of CHD were diminishing at the same time, as judged by the decline of admissions to hospital on account of sudden onset of MI.

Figure 4: Admissions to hospital in the USA on account of MI

It is interesting to note that the decline was slightly earlier in the younger age-group (<65). This suggests a cohort effect – exposure to the cause was lower or modulated in those born later.

It is also interesting to note that CHD became a milder disease during the years after about 1970, and this is born out by doctors such as myself who were in clinical practice at that time.

Figure 5: Inpatient death rate following admission for MI, USA

The milder nature of CHD can be seen in the rapid reduction in hospital mortality rate. It is remarkable now to imagine a 37% mortality rate for those admitted on account of MI in the years slightly before and after 1970. This high mortality rate was also recorded in the UK literature at the time, and I remember it well.

And so putting together Figures 3, 4 and 5, we can see that there has been a major reduction of CHD, judging from autopsy and clinical data, a major decline in the incidence of MI, and also a major  decline in the case-fatality rate of those admitted to hospital on account of MI. The result is a major reduction of overall death rate from CHD. These were also the findings of the long-term MONICA project, set up in 1973 to try to find an answer to the mysterious decline in deaths from CHD.

It is very important that in their paper Dalen and colleagues recognise that there was a true epidemic of CHD - that there was a sudden onset, a peak and then a rapid decline. It would be a great contribution to knowledge and research if the epidemic were to be acknowledged generally. There are however many “epidemic deniers”, who assume that CHD has always been present.  This means that they need not consider its emergence, but this is clearly very important if we want to understand its decline. Those who deny the epidemic of CHD are obviously completely ignorant of the very clear data.

There have been reports of arterial disease being found in Egyptian mummies. Although this has given apparent justification to the epidemic deniers, it is not the same thing as CHD and it must not imply that CHD has been continuous during the past 4000 years.. There is no reason to assume that there has been only one epidemic of CHD in recent years and particularly in the distant past.

Figure 6: The 20th century epidemic of CHD in the UK

The observation of an epidemic is clear. The next stage is speculative, to consider possible causes, to produce hypotheses that can be tested by continuing research.

This will best be developed in another post.


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Thursday, 21 January 2016

The decline of deaths from Coronary Heart Disease worldwide

The decline of the epidemic of CHD



Many of my Blog Posts refer to the 20th century epidemic of coronary heart disease, CHD. Many people must wonder if I have got it all wrong. Was there really an epidemic? Why do we not read of this "epidemic" elsewhere?  I also fail to understand this - surely other doctors and other observers must have read the original articles in the extensive medical literature. But sadly, perhaps not.

A new and recent publication in the International Journal of Epidemiology (reference at the end) was brought to my attention this week by my friend Dr Luca Mascitelli. The study looks at the decline of CHD deaths since 1980 in the countries of UK, Australia, Sweden, USA, Canada, Spain, France, Japan. 

Precise records of death require sophisticated medical services and also national public health and reporting systems. These are not always present and so it is necessary to obtain data from those countries where they do exist. The countries included in this study provide a large data set, as accurate as it is possible to be. 

It is clear from this study that there has been a major decline of age-related CHD deaths internationally, by up to 80% between 1980 and 2007. The title of the study suggests a follow-on from the Seven Countries Study, that we have seen. Now that epidemiology is much more sophisticated the new study is of much better quality and its findings are much more reliable.

The higher the incidence of age-related CHD deaths in 1980, the greater is the subsequent proportionate fall. This is an international phenomenon. There are of course countries, not in this study, in which CHD deaths do not appear to have presented an important public health problem. This could be a reporting problem but if present, then CHD would have been overshadowed by many other diseases.

The decline of age-related CHD deaths is substantial and universal, in men and in women, as shown in Figures 1 and 2.

Figure 1 CHD change in men, 1980-2007


Figure 2 CHD change in women, 1980-2007
We can also see the absolute decline, expressed as age-adjusted death rate per 100,000. In Figure 3 we see the death rates in men. Each county is represented by a series of vertical columns, each representing a period of time. All show a progressive reduction of death rate.

Figure 3: reductions in CHD death rates for men, 1980-2007

In 1980 the highest death rate from CHD was in the UK, with USA, Sweden, Australia and Canada close behind. Spain and France had lower rates of CHD deaths, and this well-known. In all countries in the study there was a major decline.

Japan is the outlier as usual with a very low number of CHD deaths. This is probably due to a high fish diet and location of most of the population at a low latitude fairly close to the equator, giving good exposure to the sun which also provides good vitamin D levels. The decline of CHD deaths was also seen in Japan, as part of the international trend.

Figure 4 shows the same trends in women. Please note that the numbers on the vertical axis are different. Compared with Figure 3 we can see that the death rate in women has been only about one third that in men. This is also well-known.

Figure 4: reductions in CHD death rates for women, 1980-2007

The decline in CHD deaths has been well and repeatedly documented. Our risk of dying from CHD is  now low, and this is why there are so many people living so long. The new epidemic is that of very old age, the elderly now being those who 40 years ago by good fortune did not not die a premature death from CHD, a fate that at that time was experienced by many. 

I stress that the mortality data are age-adjusted. There is no useful purpose in comparing the mortality rate of 50 year-olds at one time or place with 75 year-olds at another. People still die of CHD today, but they are mainly the very old, age greater than 75. We can see this clearly in Figure 5.

Figure 5: Deaths from CHD in the UK in 2010

It is interesting to note that above the age of 75 the current risk of dying from CHD is equal between men and women. Figure 5 shows the number of actual deaths in 2010 and not death rates. The equal numbers might reflect the fact that there are more women than men in this age-group.

It is clear that people below the age of 75 years, those born in the second half of the 20th century, are at much less risk, and that risk has probably diminished progressively during this time.The high risk of CHD appears to be among those born before, during or shortly after World War 2, a "cohort effect". It is as though there was during that time an environmental agent that has either disappeared or to which we have developed immunity.


The data in the study that we having been viewing started at 1980, but the death rate had been declining in the UK and the USA since 1970. The decline of stroke deaths started slightly earlier in about 1960 (Figure 6).

Figure 6: decline of cardiovascular mortality in the USA, expressed as percentage change each year

In the UK, the age-adjusted mortality rate in men in 1980, as shown in the present study (Figure 3), was 460 per 100,000, whereas in 1970 it was 520, representing 11.5% decline in ten years. 

Two important papers were presented in the UK documenting the decline of CHD between 1990 and 2002, in both men and women, and extrapolating (perhaps without justification) to the end of the epidemic by about 2020. The first was a report by the UK Government Department of Health. It was very much a "snap-shot" looking at just a twelve-year period.

Figure 7: Decline of CHD deaths in the UK, 1990-2002

The second was a paper written by Dr John Appleby, chief economist of the UK King's Fund for the study of health. He reported the decline of CHD death rates  between 1979 and 2007, comparing the UK with France. The latter started at a much lower level and so as the graph lines came together the proportionate fall in France was much less.

Figure 8: Decline of CHD deaths in the UK and France, 199-2007

But there is another aspect to the recent paper in the International Journal of Epidemiology, as appears in the title:


The low number of CHD deaths in Japan, compared to Europe, North America and Australia, was perhaps first brought to attention in the Seven Countries Study. The explanation generally given is that it is the result of a low animal fat and a high fish diet of the Japanese. The average blood cholesterol levels in Japan were also noted to be low, and these findings became an important foundation of the diet-cholesterol-heart hypothesis, which we now know to be seriously flawed and not viable.

In the present study, it was found that whereas in Japan the CHD death rate went down in men by 27% between 1980 and 2007, the average blood cholesterol level rose. This was not expected as the levels had gone down slightly in other countries. We can see the change in Figures 9 and 10. The graphs shows the average total cholesterol levels in the blood for the four age-groups shown for the years 1990 and 2008. 

Figure 9: Average blood cholesterol level by age, Japan, Men

Figure 10: Average blood cholesterol level by age, Japan, Women

This finding could have led to the conclusion that the findings in Japan, and also the worldwide reduction of CHD deaths, were incompatible with the diet-heart-cholesterol hypothesis, which would therefore be invalidated. However I suspect that this was not mentioned in the paper as such a controversial view could not be published.

The reason for the declines are usually stated to be the result of medical, pharmaceutical and public health interventions. There is no question that there has been a substantial reduction in cigarette smoking, and this was recorded in the paper. The reductions ranged between 7.1% in French men and 25.5% in Japanese and Canadian men, whereas in women there was a maximum reduction of 21.3% in Canadian women but an increase of 1.8% in French women. We can see than changes by comparing the rates in 1980 and 2012 in Figure 11.

Figure 11: cigarette smoking in 1980 in 2012, men and women


It is interesting to note the high prevalence of cigarette smoking in Japanese men. Despite this there is a very low incidence of deaths from CHD. We have already seen this in Greece, suggesting a major paradox, and now we see the Japanese extension of the Greek paradox. Where there is plenty of sun, there are few deaths from CHD regardless of cigarette smoking. Cigarette smoking cannot be regarded as the cause of CHD but it accelerates it, causing death about ten years earlier than in non-smokers.

It is also suggested that the decline in CHD deaths is due to the widespread use of statin medications. This is not likely to be the case because statins were only introduced in the 1990s. At present in the UK about 25%of people aged 70 take statins, and about 10% at the age of 50 years. We also know the small effect of statins. Even just after the height of the epidemic of CHD, in the 1980s, the benefit of treatment with a statin for five years benefitted only one in 90 very high risk men in the west of Scotland. With current much lower levels of death rate from CHD, it is likely that fewer than 1 in a 1,000 will benefit. The decline of CHD deaths would appear to have been spontaneous rather than the result of medical intervention.

The epidemic
Although there have been many descriptions of the dramatic decline of CHD deaths, such as those displayed above, these do not in themselves identify an “epidemic”. It is only when the corresponding onset  of the disease is identified that it can be called an epidemic. 

It appears to be only in the UK that good quality data are available on population mortality in the later part of the 19th and the first half of the 20th centuries, and the years leading up to 1970. These have been analysed by Dr Maurice Campbell (1891-1973), a leading cardiologist from Guy’s Hospital, London, and the first editor of the British Heart Journal. He was a highly respected physician. His important and unique work on the emergence of CHD during the 1920s seems have been forgotten - it is as though the study of CHD started only in 1980, or perhaps 1970.


Campbell’s study appeared in two short papers in the British Medical Journal in 1963. He noted the emergence of CHD in about 1924, with a doubling of deaths every few years, that is an exponential increase. He dealt with suggestions that this was just a change in diagnosis. He found evidence in the national records of an increase in total deaths from heart disease, at a time when deaths from syphilitic heart disease and rheumatic heart disease were diminishing considerably (helped by penicillin). 

I will present details of this very important work in a future Post.

We see therefore both the details of a major reduction of deaths from CHD since 1970, and also the emergence of CHD before 1970.

This data is published. Why is it not read, understood and made available to the public?

It is clear that there has been a true epidemic of CHD.

Figure 12: The 20th century epidemic of CHD in the UK


References:

Akira et al. International Journal of Epidemiology, 2015, Vol. 44, No. 5 p1614-24
British Heart Foundation. Coronary Heart Disease Statistics, 2014 edition.
Stamler J. The marked decline in coronary heart disease mortality rates in the United States, 1968-1981; summary of findings and possible explanations. Cardiology 1985; 72: 11-22.

UK Department of Health. The National Service Framework for Coronary Heart Disease: Winning the War on Heart Disease. The Stationary Office: London 2004.

Appleby J.  Does poor health justify NHS reform?  Brit Med J 2011; 342: 310

Campbell M. Death rates from diseases of the heart: 1876 to 1959. Brit Med J. 1963; 2: 1963. 
Campbell M. The main cause of increased death rate from diseases of the heart: 1920-1959. Brit Med J. 1963; 2: 712-717. 
Grimes DS. An epidemic of coronary heart disease. Quart J Med 2012; 105: 509-518.