Higher cholesterol levels associated with lower risk of death from cardiovascular disease in Japan

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 [1]. 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 [2]. 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 [2] 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

12 Responses to Higher cholesterol levels associated with lower risk of death from cardiovascular disease in Japan

  1. TerryJ 8 July 2011 at 3:07 pm #

    Typo in the title “assocatiated”

  2. John Briffa 8 July 2011 at 4:08 pm #

    Thanks Terry – corrected now.

  3. Alan Watson 8 July 2011 at 6:06 pm #

    In the early ’50s, the Japanese had low calorie, low fat (5% of calories), low refined sugar diets. They also had low rates of heart disease; high rates of stroke. Twenty years later, in the ’70s,as they prospered, their intake of fat had increased to 20% of calories (carb calories went down) and mortality from stroke went down dramatically. (I read this in the book Cholesterol Con by Malcolm Kendrick, MD.

  4. John Vickers 8 July 2011 at 7:12 pm #

    Very interesting post. I do have a question on it though, it doesn’t mention the type of cholesterol. Do you have a breakdown on LDL/HDL/triglyceride?

    My wife is type 1 diabetic; she went to the hospital recently and was told her cholesterol levels are too high (5.4), and that a type 1 diabetic should have a cholesterol level below 4. Triglycerides were less than 0.5!



  5. D. 8 July 2011 at 7:22 pm #

    I have read several times recently that “dietary” factors don’t play a part in whether or not your cholesterol is high or low. What, then, does affect cholesterol levels? I am from America and we measure differently than the Brits, but my total cholesterol was, at one point, 139. Too low! I want to get it up over 200 if possible, but if eating doesn’t change the composition of blood cholesterol, how do I go about raising that number to a healthier 200+ ? I’m confused.

    I also had my homocysteine level checked and it was fine (if you can truly rely on these blood tests, that is). I am more concerned about that number than total cholesterol. So then, another question — if homocysteine is fine, do I need to worry about total cholesterol? I’m not a bit concerned with HDL and LDL because those numbers are less important, as far as I’m concerned.

    I have a prolapsed mitral valve and am trying to wean myself totally off of the beta-blocker (I’m down from 100 mg to 12.5 mg of Tenormin daily) but I can’t seem to find a more natural substitute for beta-blocker. I’m thinking if my cholesterol numbers where a bit higher, I might not need the Tenormin at all because the PMV would possibly correct itself. This PMV started as a murmur of pregnancy and didn’t go away. Am I on the right track, do you think?

  6. Gill Oliver 25 August 2011 at 8:37 pm #

    Does this mean that statins can help healthy individuals with low cholesterol (not to have strokes ..heart attacks)?? Statins reduce the risk of cardiovascular disease in people with normal to low cholesterol.Would it not be prudent to take them for this reason only?

  7. Marcel 25 November 2012 at 10:11 pm #

    Great article.
    Do these facts also apply for the middle cholesterol bands?

  8. Rob 19 January 2014 at 7:14 am #

    This is all well and good but the fact remains that the healthiest, longest-lived populations have cholesterol in the “less than 4.1 mmol/L” category. The only population I could find with elevated cholesterol levels and good longevity was the Swiss. However, they live in a high altitude, which lowers LDL. They also have a high standard of living in that country and an excellent health care system. A country’s economic status will have an impact on the health of its people.


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