Dr. Malcolm Kendrick

Cholesterol goes up heart disease goes down

As readers of this blog will know well, I do not believe that cholesterol levels have anything to do with heart disease, which would more accurately called coronary artery disease (CAD) or coronary heart disease (CHD). This is not a view that is widely accepted in the medical community, nor in society as a whole. In fact, this view places me very firmly in the ‘nut job’ category. I have been told that my views mean that I feature on several quack watch sites. Hoorah, fame – of a kind – at last.

So when I come across information that supports my position, I am always keen to make as much noise about it as possible. Today, or at least today as I write this, someone sent me an article entitled ‘Continuous decline in mortality from coronary heart disease in Japan despite a continuous and marked rise in total cholesterol: Japanese experience after the Seven Countries Study.

Now, that’s the kind of thing that I like to see. Cholesterol levels go up; heart disease rates go down. Here is the abstract of the paper, published in the International Journal of Epidemiology:

The Seven Countries Study in the 1960s showed very low mortality from coronary heart disease (CHD) in Japan, which was attributed to very low levels of total cholesterol. Studies of migrant Japanese to the USA in the 1970s documented increase in CHD rates, thus CHD mortality in Japan was expected to increase as their lifestyle became Westernized, yet CHD mortality has continued to decline since 1970. This study describes trends in CHD mortality and its risk factors since 1980 in Japan, contrasting those in other selected developed countries.

We selected Australia, Canada, France, Japan, Spain, Sweden, the UK and the USA. CHD mortality between 1980 and 2007 was obtained from WHO Statistical Information System. National data on traditional risk factors during the same period were obtained from literature and national surveys.

Age-adjusted CHD mortality continuously declined between 1980 and 2007 in all these countries. The decline was accompanied by a constant fall in total cholesterol except Japan where total cholesterol continuously rose. In the birth cohort of individuals currently aged 50–69 years, levels of total cholesterol have been higher in Japan than in the USA, yet CHD mortality in Japan remained the lowest: >67% lower in men and >75% lower in women compared with the USA. The direction and magnitude of changes in other risk factors were generally similar between Japan and the other countries.

Conclusions: Decline in CHD mortality despite a continuous rise in total cholesterol is unique. The observation may suggest some protective factors unique to Japanese.’1

This paper was actually published in July, but I missed it until now. I have to say that I like everything about the abstract (and the entire paper) apart from the last ten words. ‘The observation may suggest some protective factors unique to Japanese.’ You may be thinking, what’s wrong with that suggestion. It seems completely reasonable.

I put it to you, members of the jury, that we have a situation whereby we see continuously rising cholesterol levels in a population, whilst the rate of heart disease in that population (already very low), falls even lower. This, despite the fact that their other risk factors are just as high, if not higher than in all the other countries studied. Just to compare and contrast Japan with the USA and the UK. These figures are from the latest year 2008 where all figures are available (figures for men).

COUNTRY JAPAN UK US
% WHO SMOKE 35.4% 23% 17.2%
AVERAGE BP (SYSTOLIC) 130.5mmHg 131.2mmHg 123.3mmHg
CHOLESTEROL LEVEL 5.2mmol/l 5.4mmol/l 5.1mmol/l
% OF POPULATION WITH DIABETES 7.2% 7.8% 12.6%
RATE OF CHD/100,000/year 45.8 143.7 150.7

Perhaps most important thing in this study is that the rate of CHD in men in Japan was 62.4 (per 100,000/year) in the years 1980 – 83, when their average total cholesterol level was 4.8. Since then cholesterol has risen 9% to 5.2mmol/l; meanwhile the CHD rate has fallen by 27%. In fact, this trend of rising cholesterol and falling CHD has been going on since the 1960 – which is also mentioned in this paper2.

More dramatically, the rate of stroke in Japan, which was once the highest in the industrialized world, has dropped by more than 80% over the last fifty years, or so. Most people bring together deaths from coronary heart disease, and stroke, under the overall banner of cardiovascular disease (CVD). Raised cholesterol is considered a major risk factor for both, and statins are prescribed for both. Yet, as cholesterol levels have steadily risen in Japan, deaths from both major forms of CVD have fallen massively.

Where was I. Oh yes, I was putting it to the jury that the evidence from Japan utterly and completely contradicts the cholesterol hypothesis. Utterly and completely. Facts like these should leave the hypothesis as a smoking ruin. But of course, this has not happened, as it never does.

Karl Popper, the famous scientific philosopher, would say that such a finding represents a black swan. If your hypothesis is that all swans are white, finding more and more white swans slightly strengthens the likelihood that your hypothesis is correct. However, if you find one single black swan, your hypothesis is wrong and must be discarded.

Unfortunately, a recurring theme in medical research is that, when someone does discover a black swan, the medical experts immediately come out and tell you that this black swan is not, in fact a black swan at all. It is a swan that may look black but it will, in time, turn out to be have been white all along. A more bullish tactic is to state that, as all swans are white, a black swan cannot be a swan at all. It is a member of a different class. ‘The black bird that looks exactly like a white swan.’

Both approaches come under the banner of ‘Our hypothesis is right, we absolutely know that it is right, so any evidence that contradicts our hypothesis must be wrong.’ Or can be explained away. Otherwise known as painting the black swan white.

Explaining away also comprises a few other, well established, techniques. Firstly, to denigrate the researchers, or their research. They didn’t measure this correctly, the ignored that, they can’t be trusted, this is rubbish work – please ignore. I call this technique ‘kill the unbeliever.’

The next form of explaining is to call your finding a paradox. i.e. we know that this looks just like a black swan, but an explanation will be found at some time for its apparent blackness. Let us simply ignore this finding until the correct explanation comes along to explain it. I call this technique ‘Hide the black swan away in a cupboard and hope everyone forgets it was ever there.’

Fortunately, or unfortunately, depending on your position on the cholesterol hypothesis, these techniques won’t really work here. This study was funded by the National Institutes for Health, which makes it difficult to rubbish the results, or the researchers. Also, the data have been gathered by the WHO under the MONICA study. A massive and high quality data set which I have never seen anyone argue with. It was also published in the International Journal of Epidemiology. Generally considered a high quality medical journal.

Equally, it is rather difficult to call the Japanese data a paradox. We are not looking at a sudden, one-off finding. What we have in Japan is over sixty years of data, all pointing exactly the same way, year after year. The Japanese cholesterol levels have gone up, year on year, and there has been a steady (yet massive overall) reduction in the rate of heart disease and stroke. This data comes from a population of over one hundred million. Sorry guys, this Paradox hasn’t gone away.

It is also exceedingly difficult for mainstream researchers to attack this current data, as the Japanese were once held up as poster boys for the cholesterol hypothesis. ‘Look at the Japanese’ the researchers shouted loudly in the 1960s. ‘Very low cholesterol levels and very low rates of heart disease… case proven.’ In fact, the Japanese data were one of the strongest drivers of the cholesterol hypothesis. It is entirely possible that, without the Japanese data, the cholesterol hypothesis would never have been accepted in the first place.

Well, look at the Japanese today. Not shouting about them from the rooftops now, are we chaps? Sorry, what was that…couldn’t quite hear you. You may be thinking, at this point. Ah, so the Japanese must be genetically protected against heart disease. Well, this is not correct. To quote from the paper again:

‘Studies of migrant Japanese to the USA in the 1970s reported a dramatic increase in CHD rates within one generation of migration. It was thus expected that exposures to more a Westernized lifestyle among native Japanese after World War II (WWII), for example increase in dietary intake of saturated fat, would cause sizeable rise in blood total cholesterol, leading to a considerable increase in CHD rates in Japan. Between 1960 and 1990, dietary intake of fat and cholesterol in Japan more than doubled. The current levels of blood total cholesterol in Japan, especially among individuals born after WWII, are comparable to those in other developed countries, very different from the 2-mmol/l difference in total cholesterol at the time of the Seven Countries Study.

Moreover, age adjusted mortality from other diseases related to Westernized lifestyle, such as colon, breast and prostate cancers, more than doubled during this period. Very surprisingly, age-adjusted CHD mortality in Japan started to decline in 1970 as in Western countries, and has remained one of the lowest in developed countries: >67% lower in men and >75% lower in women compared with the USA, accounting partly for the greatest longevity in the world among Japanese.’

I liked the words ‘very surprisingly’ in that section. There is only one reason why you should be very surprised in science. That is, when everything you thought you knew about something proves to be wrong.

Just to summarize here. The data from Japan are robust, the researchers free from commercial bias. We are not looking at poor quality research, nor are we looking at a paradox, it is a pure black swan. Yes, of course, the researchers tried to find something, anything, that could explain away this finding. They looked at salt intake. Ooops, the Japanese have way higher salt intake than every other country they looked at. Sorry, ignore.

They did find that the Japanese ate more fish than in most other countries and that, my friends, was that. In fact, even they didn’t believe that this provided any explanation. For we are left with this statement at the end of the discussion section:

The lower CHD mortality in Japan compared with the USA is very unlikely to be due to the difference in trends in other CHD risk factors, cohort effects, misclassification of causes of death, competing risk with other diseases or genetics. The observation may suggest some protective factors unique to Japanese which merit further research.’

I shall give you a different conclusion from this study. One that actually fits the facts that these researchers round.

‘A raised cholesterol level is not a cause of CHD/CVD. ‘

There you are, nice and simple. There is no need for the creation of unknown and undiscovered ‘unique’ protective factors. It just fits. And when a hypothesis fits all the facts, without the need for any fancy adaptations, you know that it is right. That, my friends, is called science.

 

References
1:  Continuous decline in mortality from coronary heart disease in Japan despite a continuous and marked rise in total cholesterol: Japanese experience after the Seven Countries Study’ International Journal of Epidemiology, 2015, 1614–1624 due: 10.1093/ije/dyv143

2:   Ueshima H, Sekikawa A, Miura K et al. Cardiovascular disease and risk factors in Asia: a selected review. Circulation 2008;118:2702–09.