We’re constantly reminded that having a ‘raised’ cholesterol level puts us in mortal danger of cardiovascular diseases such as heart disease and stroke. Several times I have covered evidence which strongly suggests that cholesterol is not the killer it’s made out to be.
One major line of evidence here is the fact that reducing cholesterol does not appear to have broad benefits for health. A review some years ago found that while statins (the most commonly prescribed cholesterol reducing drugs) have the capacity to reduce overall risk of death, other fat-modifying drugs such as fibrates and resins do not . And neither does taking dietary steps to reduce cholesterol. And neither does taking a newer cholesterol-reducing drug by the name of ezetimibe.
Could it be, then, that the way statins reduce the risk of cardiovascular disease has nothing to do with cholesterol? Actually, apart from their cholesterol-reducing effects, statins are known to have several different actions that could, theoretically, reduce risk of cardiovascular disease. In other words, the beneficial effects of statins might have nothing to do with the fact that they reduce cholesterol.
We have some evidence which supports this notion. For example, statins reduce the risk of cardiovascular disease in people with normal or low levels of cholesterol. Also, statins significantly reduce the risk of stroke, even though cholesterol is a weak or non-existent risk factor for stroke.
I was thinking about these things when reading a research letter in a recent edition of the Archives of Internal Medicine . The letter was primarily concerned with the relationship between cholesterol levels and the risk of stroke in Japan. Before we look at its findings, let’s go through some basics regarding the different types of stroke.
Strokes are caused when blood supply to the brain is interrupted for a prolonged period of time. There are two main ways this can happen. In one type of stroke, known as ‘haemorrhagic’ stroke, blood vessels burst and bleed. In the other main type, known as ‘ischaemic’ stroke, blood vessels become blocked.
Ischaemic strokes come into two main subtypes. In one of these, blockage is caused by a combination of atherosclerosis and blood clotting – these are known as ‘atherothrombotic’ strokes. In others, small blood clots can form in the heart, which then travel to the vessels in the brain causing blockage – these are referred to as ‘cardioembolic stroke’.
One of the points made in the research letter  is that in Japan, cardioembolic strokes are quite common, relatively speaking. And there is some link between low cholesterol levels and a heart rhythm disturbance known as atrial fibrillation. The relevance of this is that atrial fibrillation is a risk factor for clot formation in the heart and cardioembolic stroke. Could an increased risk of cardioembolic stroke associated with low cholesterol outweighs the supposed reduced risk of atherothrombotic stroke? In other words, could the problems associated with low cholesterol outweigh its supposed benefits?
The author of the piece, Dr Hisako Tsuki of Kansai Medical University in Japan, presented data for risk of stroke at different levels of cholesterol in more than 16,500 people followed for about a decade. Cholesterol levels were split into four bands:
less than 4.1 mmol/L
4.1- less than 5.2 mmol/L
5.2- less than 6.2 mmol/L
greater than 6.2 mmol/L
The results showed that risk of death from ischaemic stroke was reduced by 71 per cent in individuals within the highest cholesterol band compared to the lowest. Also, the higher the cholesterol, the lower the risk. In other words, it seems as though the problems associated with low cholesterol do indeed outweigh any benefits where ischaemic stroke is concerned.
The results for haemorrhagic stroke were even more startling, though: The risk in the highest cholesterol band was 96 per cent lower than the lowest band. Again, the higher the cholesterol, the lower the risk.
Taking all forms of stroke together, risk of death in the highest cholesterol band was 77 per cent lower than in the lowest band.
Of course we’re told that raised cholesterol causes heart disease, so maybe higher cholesterol causes problems here that outweigh any benefits with regard to stroke. Actually, this research found no significantly increased risk of death due to heart disease in those with the highest levels of cholesterol.
So, what happens when all of this data is put together and the relationship between deaths due to cardiovascular disease (heart disease and stroke) and cholesterol is calculated?
The results showed that the higher someone’s cholesterol was, the lower their risk of death due to cardiovascular disease. In those with the highest cholesterol, risk of death was 58 per cent lower than those in the lowest cholesterol band.
It is possible that this data is specific to the Japanese, because they have relatively high levels of stroke relative to heart disease. But even if that’s the case, the fact that higher cholesterol was not associated with an increased risk of death from heart disease and an increased risk of the two main forms of stroke is noteworthy and deserves to be reported, I think. Actually, I’ve not heard or seen a peep about this research – anywhere. Of course, if you buy wholeheartedly into the cholesterol hypothesis, then perhaps the only thing you can say is nothing at all.
1. Studer M, et al. Effect of different antilipidemic agents and diets on mortality: a systematic review. Arch Intern Med 2005;165(7):725-30
2. Tsuji H. Low serum cholesterol level and increased ischemic stroke mortality. Archives of Internal Medicine. 2011;171(12):1121-1123