Posted by on Saturday, 23 July 2016

Cholesterol confusion and climate change

Photo by Malcolm Koo (Creative Commons)
There are two types of people in the world - those who repeatedly suggest there are two types of people in the world and those who don't.

When it comes to cholesterol and heart disease however, there seem to be three types of people in the world: Firstly those who think fat is bad, cholesterol causes heart disease and statins should basically be put in the water supply; Secondly those who suggest cholesterol is a natural healthy substance, saturated fat is fine and doesn't affect serum cholesterol anyway and that statins are at best ineffective and at worst part of an evil plot by Big Pharma to make vast sums of money and hang the consequences to anyone who takes them. Thirdly there is the group that watches the two extremes bicker and squabble. That reads report after report each debunking the other's 'evidence' shrugs our shoulders and wonders what on earth to make of it all.

You may be able to tell that I am firmly in the third group.

I have tried to write this post many times before. Almost always after the release of some study or other which shines light on it (from either direction) in a pretty conclusive way. But each time this happens, almost without fail, within a day or two I will see something else that eloquently argues exactly the opposite point of view - and I find myself back at square one. So I have given up waiting until I have made up my mind one way or another and decided to just pour it all out. To try to explain my confusion - probably mostly to myself. It will be rambling, contradictory, borderline-incoherent, and in reality I should probably re-read it and get rid of at least two thirds of it. But I'm not going to spare you that, dear reader. You will just have to suffer along with me.

At the outset it is crucial to remind you that I have absolutely NO medical expertise whatsoever. This is not advice (perish the thought!). I don't understand most of this stuff enough to apply it to my own situation, let alone anyone else's. I know people that take Statins and get on well with them. I know people that have had terrible experiences with Statins and would not touch them with a bargepole.

The last time I nearly wrote this post was April this year when I read this report of the HOPE trial. I found this particularly interesting, because it talks specifically about 'primary prevention'. That's medical shorthand for giving people some medicine to prevent a thing happening that they might be at increased risk of.
“Statins work beautifully, resulting in a high significant relative risk reduction of 25%,” said Yusuf. Further, statins were “relatively safe,” though there was a small excess in muscle pain, but not rhabdomyolysis, in the statin-treated group.
Wow! 25% less chance of heart attack or stroke. Sounds pretty worthwhile. And HOPE-3 focussed on a population at 'intermediate risk'. So these are benefits that were shown to exist even where increased risk was only fairly modest. This caught my eye because you don't have to live with type 1 diabetes for long before people start telling you that you are going to die of a heart attack. That's what does for most of us, apparently. However perky your blood glucose management is generally, living with T1 you will almost certainly be having significant glucose excursions that 'nonnys' would never have. Of course you can significantly reduce your theoretical risk by keeping a lid on your blood glucose levels and HbA1c - but therein lies the snag for people trying to view any of this research and apply it to their own situation. Risk calculators don't work if you have T1. And primary prevention studies that take a cohort of people with a UK-average HbA1c of 9% or so, might have a different risk to you as an individual depending on your own fortunes wrestling the Diabetes Gremlins. Benefit shown to those at 'intermediate risk' was certainly interesting though. I've not had a heart attack, I'd like to keep it that way and I'm getting older year by year.

I had promised my clinic that I would continue to keep an open mind about the cholesterol issue, and perhaps this was it - the primary prevention study I had needed to convince me that it was worth trying a Statin and seeing how I got on with it, in the hope that my undoubted increased risk of heart-based shenanigans might be reduced by 25%.

The elephant in the room, of course, is the term 'relative risk'. Studies, particularly Statin studies, are quite keen on using that frame of reference as it usually gives a nice Big Attention Grabbing Number. So if your risk of something happening was 0.1% and it dropped to 0.08% it might sound pretty meagre. But you could express the same change as a 20% reduction in relative risk, which sounds much more weighty. Hmmmmmmm.

Hot on it's heels, if not chronologically but more in terms of the way I stumbled across things was this rather sensationalised tabloid reference to a study by Professor Harumi Okuyama, of Nagoya City University, Japan. This time, taking Statins can actually apparently *make things worse*. Harden your arteries and increase your risk of heart attack.

This was followed swiftly by this piece by Cardiologist and confirmed Statin sceptic Dr Aseem Malhotra which raises some well-worn questions over the entire evidence-base behind cholesterol-lowering drugs and the refusal of the companies to release the raw data on side-effects.
"biased reporting in medical journals, commercial conflicts of interest and medical curricula that fail to teach doctors how to understand and communicate health statistics was contributing to an epidemic of misinformed doctors and misinformed patients."
reputed French Cardiologist Dr Michel De Lorgeril's own analysis reveals that all studies published after 2006 reveal “no benefit” of statins for cardiovascular prevention in all groups of patients.
I'm not even going to open the can of worms that links Statins prescribed to people without heart disease and a doubling of their risk of developing Type 2 Diabetes. Frankly I have enough on my plate with the diabetes I already have.

And again here, from just this week. Another article that confidently suggests nails in the coffin of the cholesterol hypothesis.
Dr John Abramson, a health policy expert from Harvard Medical School, looked at the HOPE-3 trial and told me the effects were meagre indeed: “91 people have to be treated with a statin for 5.6 years in order to prevent 1 non-fatal heart attack or stroke.” Another way to say this is 90 of the 91 people who take statins for that long won’t see a benefit (and some will experience adverse side effects).
The observant among you will be smiling that exactly the same HOPE trial mentioned above with glowing 25% reductions in risk and very low side effects is now being interpreted as having almost no effect whatever *except* the possibility of side-effects. Though of course, for the 1 person out of 91, the 'not having had a heart attack' would probably be seen as quite a benefit. I wonder how you get to know that you are that 1 person and not one of the other 90. How exactly you notice that something is not happening to you because of a tablet rather than it just not happening to all the others.

And yet... and yet... Most doctors and scientists in the world seem to remain convinced of the link between heart health and lower cholesterol.

My basic problem
Over the last 4 or 5 years I have read a number of posts and articles from people who raise questions over the whole lipid/fat/cholesterol/heart hypothesis. I know that for some of you this will ring alarming tin-foil-hat klaxons, but articles like this (higher cholesterol associated with lower mortality overall *including* heart disease) and this (what causes heart disease anyway) are an entertaining read - and I cannot help it - but they do seem make a lot of sense to me.

I know that for some (many? most?) healthcare professionals some of these characters are a sort of... well, if not exactly laughing stock - certainly not voices to be taken seriously. People who insist that everyone else has it wrong and only they know the truth. Eyes roll. "OK then, if you say so. Never mind dear."

Perhaps it is precisely because I am not medically educated, that I have not learned and trusted the basics of the 'status-quo'. I have less invested in one way of thinking about cholesterol and heart health - and so it is easier for me to read these other arguments and think, 'Well that's interesting.'

Of course, proponents of the mainstream viewpoint will point to decades of scientific research and understanding that have brought us to where we are. For them the lipid-heart hypothesis is an unshakeable fact. And this or that or the other study* has shown that lowering cholesterol really does work. Most of their peers think the same. So take your tablets and feel safer.

*('Funded and published by the people that make the tablets!!' cry the sceptics)

And around and around I go...
  • Lots of studies over many years show (apparently) convincing benefit of Statins for heart disease with very low risk of side effects
  • Sceptics say the 'adverse event' data are under-reported and the pharma companies refuse to release the raw information for independent analysis
  • When it comes to secondary prevention (people who have already had a heart attack) the evidence is much clearer. Most people seem to agree that they work and work well
  • Even among cholesterol sceptics or neutrals there is a thought that it might be some activity of Statins other than cholesterol reduction (such as reduction of inflammation or stabilisation of plaques) that confer benefit
  • Statins are the most profitable drug in the history of the world - vested interest doesn't even begin to cover it
  • And yet I do not subscribe to the view that All Big Pharma Is Evil either - of course pharmaceuticals is a business and the companies have a requirement to make money for their stockholders - but I do think that it is in their interest to create 'products' actually help people, those will be much easier to shift after all
Climate change
The other day, all this made me think about climate change. A decade ago there was a funny little film by Davis Guggenheim and Al Gore called 'The Inconvenient Truth'. We don't even think about it much any more really. As I am sure many of you will remember, the eponymous 'truth' was that the actions of the human race had built up over time and were affecting the climate of the entire planet. Greenhouse gasses, climate change and all that. What struck me was the way that the voices that first raised these ideas from as early as 1896 were initially dismissed perhaps even ridiculed for their line of thinking. Not only that, but now that global warming has been firmly adopted into the scientific mainstream there are still contrary voices. Voices who will insist that for all the evidence that it is unmistakeably happening all around us that climate change is Nothing To Do With Us. That the whole thing is a hoax. A scam. Deniers who will wrap their arguments in convincing-seeming scientific language of planetary cycles, solar variation and internal radiative forcing. There's a conspiracy theory for everything it seems.

And I wonder where we are with cholesterol and heart health? Who is on which side? Will the ones who are being ridiculed ultimately turn out to have got it right? Or at least, made steps in the right direction? Will the mainstream position change in the light of more and better and more independent evidence? Or has the mainstream got it right already and are the cholesterol-deniers just confusing everyone.

I really wish I knew the answer. Because however many times I try to unpick this I always end up here. Shrugging and thinking... well I don't know! Which doesn't really do enough to convince me to take a tablet every day for the rest of my life.


  1. Great article Mike and one of interest to me, from a general point of view, not a T1 point of view.

    A couple of years ago my cholesterol was 2.58, pretty impressive I thought.
    Last year it was 6.1, pretty worrying I thought, that is until you seen the breakdown and use the numbers in calculations found everywhere - here and and loads more places . To any calculation ratios are currently excellent although I'm flouting the higher limits for cholesterol.
    Is my heart in good health though? Who knows?
    Are the values/ratios in the first article correct, relevant and useful. Who knows?
    There's four types of people in the world, one being those who have recently joined group 2 but wonder after years of being in group 1 whether they've joined a mumbo-jumbo-new-age-cult that will be proved to be idiots in years to come.

    1. Haha! Thanks Kev - I know just what you mean. And the more you look into component parts of the lipid panel the more bizarre and confusing it becomes. Total cholesterol counts for little, it seems, even to those who are still in 'group 1'. And LDL, despite its 'bad cholesterol' billing is not cholesterol, is only ever estimated in our figures not measured directly, and is fundemental to many processes in brain and muscles so one wonders how low is too low. VLDL seems to be the nasty particle that could 'scour' the inside of a vessel, but that isn't measured or estimated. Seems that the Trigs measure is the best guide to VLDL, though confusingly it is a measure of something called triglycerides, but which are not triglycerides. It is at this point I usually give up!

  2. Just a few points:

    1. In some respects it doesn't matter how statins work - they lower cardiovascular risk substantially. The cholesterol /diet / fat debate is almost a separate issue.
    2. The risk of side effects are low - and if they occur, an alternative statin will often overcome this problem.
    3. Relative risk and number needed to treat are relevant but the problem is you can't accurately predict which individuals will have an MI and when. You have to use population estimates.
    4. You need to balance risk of side effects vs. Benefit of treatment. If my risk of a heart attack is estimated at 5% over ten years and I can lower that to 3% with a statin - my judgement call is 'take the statin'. Most side effects are mild and often avoidable (change statin, twice weekly dosing etc.). Heart attacks and strokes: not so 'mild'.
    4. Current guidelines are based on cost not effectiveness - why not take a statin if ten year risk 7% and se risk substantially lower.
    5. The statin critics are a small band of individuals who make a career out of this. The cardiologist you mention does not strike me as an academically impressive individual. I think he has more Today programme appearances than first/final author original studies.
    6. Us NHS diabetologists don't get paid to prescribe these drugs!
    7. Ultimately if risk of taking drug < benefit - take the drug. Unfortunately a good RCT in T1DM won't be reported any time soon.

    1. Many thanks for your comments Anon. Very helpful. I absolutely agree - if side effects are rare or mild then it becomes a very easy decision. The weird thing is how often side effects get discussed in patient communities and the impression is that they are significantly less rare and more debilitating than the official figures suggest. I suppose that is what weighs heavily on my mind. that and the high number of people who stop taking statins after starting, because of perceived side effects. I understand entirely that even people taking placebo in trials can report side effects, but for statins there does seem to be something of a cloud of voices that do not quite tally with the published information, the raw data of which remains under lock and key.

      Still, you give a very useful round-up and much food for thought. Thank you.

    2. Incidentally Anon, if you don't mind me asking - I wonder if you take a statin yourself?

  3. Really good post! Thank you for sharing. My endo suggested statins as a preventative measure at my last visit but I'm not ready yet! I don't want to be old:-/

    1. Really enjoyed your post! I also think I'm in the 3rd category it made me laugh when I read that.

  4. What an excellent article Mike.

    I think we should make more of the evidence that exercise and diet have on the lipid profile, particularly the ability to lower the (bad) LDL fraction.

    Here's a good meta-analysis from the Journal of the American Heart Association, 2015:

    I know I'd much rather explore that route first than have to take a daily statin.

    As always, take the decision jointly with your physician.

    And this is a lovely video of Dr Ellsworth Wareham - a wonderful cardiothoracic surgeon who retired at the age of 95! He attributes this to his healthy vegan lifestyle - and philosophy on life.

    Very best wishes,