Before looking at the connection between blood cholesterol levels and heart disease, I think it is worth highlighting a critically important – remarkably unheralded – fact: after the age of 50, the lower your cholesterol level, the lower your life expectancy. Perhaps even more important than this is the fact that a falling cholesterol level sharply increases the risk of dying, of anything, including heart disease.
The dangers of a low cholesterol level were highlighted by a major long-term study of men living in Honolulu: ‘Our data accord with previous findings of increased mortality in elderly people with low serum cholesterol, and show that long-term persistence of low cholesterol concentration actually increases the risk of death.’
The danger of a falling cholesterol level was first discovered (somewhat ironically) in the Framingham study: ‘There is a direct association between falling cholesterol levels over the first 14 years [of the study] and mortality over the following 18 years.’
It seems almost unbelievable that warnings about the dangers of a high cholesterol level rain down every day, when the reality is that a low cholesterol level is much more dangerous than a high level.
Given this, why would anyone want to lower the cholesterol level? On the face of it, it would make more sense to take cholesterol-raising drugs. Especially after the age of 50.
Cholesterol Levels and Heart Disease
The reason why everyone is so keen to lower cholesterol levels is that supporters of the hypothesis have decreed the following:
A high level of cholesterol causes premature heart disease.
A low level of cholesterol is caused by an underlying disease. It is the underlying disease that kills you, not the low cholesterol.
Therefore, if you lower the blood cholesterol level you will reduce the risk of heart disease, and you will not increase the risk of dying of any other disease.
FIGURE 3
This could be true, but it is worth reviewing some of the evidence that linked raised cholesterol levels to heart disease in the first place. Let’s begin with women.
Perhaps the largest single analysis of cholesterol levels, and death from cardiovascular disease (and other diseases), was published in 1992. This review included more than 100,000 women, aggregated from a number of different studies and countries.
To quote from the study, ‘The pooled estimated risk for total cardio-vascular death in women showed no trend across TC [total cholesterol] levels.’ In short, for more than 50 per cent of the world’s population – women – raised cholesterol is not a risk factor for heart disease.
Moving to men, it is true that under the age of 50 there does seem to be an association between raised cholesterol levels and heart disease. But, after that age, when more than 90 per cent of heart attacks happen, the association disappears.
In addition, those populations in the world with the highest rates of heart disease in younger men – including emigrant Asian Indians, Eastern Europeans, Native Americans and Australian Aboriginals – tend to have significantly lower cholesterol levels than the surrounding populations/countries.
Perhaps the single most directly contradictory fact is that, in young Japanese men, the average cholesterol level has risen over the last 20 or so years, yet the rate of heart disease has fallen. As with many facts in this area, if they don’t fit the cholesterol hypothesis, dismiss them.
Lowering Cholesterol Levels With Drugs
Surely, despite everything written up to this point, all previous arguments are refuted by the knowledge that lowering cholesterol levels with statins protects against heart disease. As all good scientists know, ‘reversibility of effect’ provides the most powerful supportive evidence for a hypothesis.
However, the flipside to this argument is as follows. How can lowering cholesterol levels prevent heart disease in people who do not have a high level? The most often-quoted clinical trial in the last few years is the UK-based Heart Protection Study (HPS). A veritable triumph for statins, demonstrating protection in almost every group studied.
What is most intriguing, however, is that protection was apparent if the starting cholesterol level was high, average or low. How can this be explained? At this point we enter Alice in Wonderland territory. A rational person would accept that a normal cholesterol level cannot be a risk factor for heart disease (or anything else for that matter). Therefore, people with normal cholesterol levels can gain no benefit from having their levels lowered.
So, if statins do protect those with normal, or low, cholesterol levels – which they clearly do – they must be doing this through some other mechanism of action, unrelated to cholesterol lowering. In fact, there is a growing body of evidence to support the idea that statins have a whole series of different protective actions.
However, accepting that statins work ‘in another way’ would demolish the final buttress keeping the cholesterol hypothesis afloat. And so the latest argument is that no one in modern society has a normal cholesterol level. An article in the Journal of the American College of Cardiology best sums up this line of thinking. Under the heading, ‘WHY AVERAGE IS NOT NORMAL’, O’Keefe, the lead author, makes the claim, ‘Atherosclerosis is endemic in our population, in part because the average LDL [low-density lipoprotein, or ‘bad’ cholesterol, of which more later] level is approximately twice the normal physiologic level.’ In short, according to O’Keefe, our cholesterol level should be about 2.5 mmol/l, not 5.2 mmol/l.
This argument, if true, does neatly demolish the question, ‘How can people with normal, or low, cholesterol levels be protected against heart disease?’ O’Keefe and others would argue that we all have a high cholesterol level. Everyone is ill, and all shall have statins.
One oft-quoted fact that seems superficially supportive of O’Keefe’s hypothesis is that peasant farmers in China have very low cholesterol levels and a very low rate of heart disease (although their average cholesterol levels are actually about 4, not 2.5).
But, when you study the figures with more care, they reveal something else. As usual, those with low cholesterol levels have by far the highest mortality rates. Liver failure and liver cancer are common causes of death. However, there is a simple explanation for this association.
Many Chinese peasant farmers have chronic hepatitis, which creates low cholesterol levels, and also leads to liver failure and liver cancer, which is why people with low cholesterol levels die young.
Does this mean that a low cholesterol level protects against heart disease? No. What the Chinese data tell us is that those with higher cholesterol levels are not chronic-hepatitis carriers, so they live longer and have more chance of developing heart disease in old age. On the other hand, those with low cholesterol levels cannot die of heart disease, because they are already dead.
Without chasing too many mad arguments around, the simple fact is that everyone in the West does not have a raised cholesterol level. Repeated studies have shown that a perfectly normal or healthy cholesterol level lies between about 4 and 6, and lowering it cannot protect against heart disease, otherwise we will have introduced a new concept into medical science. Normal is unhealthy and must be treated.
People are grasping at straws in their attempt to explain why statins protect against heart disease in those with normal cholesterol levels, and in women and the elderly, where a raised cholesterol level is not even a risk factor. The only possible explanation for the results of the statin trials is that statins do not work by lowering cholesterol levels.
The cholesterol hypothesis is a complicated mess
The cholesterol hypothesis has always exuded the siren song of simplicity. However, once you start to examine