More evidence that ‘modifying’ cholesterol does not necessarily have broad benefits for health

Higher levels of so-called ‘HDL-cholesterol’ is associated with reduced risk of cardiovascular issues including heart disease and stroke. This finding has led to the widespread view that raising HDL levels has benefits for health, particularly with regard to cardiovascular risk.

There are three main classes of agents that are known to boost HDL levels: the B-vitamin niacin (vitamin B3), fibrates, and inhibitors of what is known as ‘cholesteryl ester transfer protein’ (CETP-inhibitors). Recently, a review of the impact of these agents on health was published in the British Medical Journal [1].

The review assessed data from studies which had compared the impact of these agents on their own, or when added onto treatment with statins.

When added to statins, none of the agents brought any benefits in terms of endpoints such as non-fatal heart attack, fatal heart attack or overall risk of death (overall mortality).

When not taken in conjunction with statins, however, niacin and fibrates were found to reduce the risk of non-fatal heart attack (but there were no mortality benefits). CETP inhibitors did no good in any setting, and one CETP (torcetrapib) actually increased the risk of death (it has been withdrawn from sale).

An accompanying editorial [2] from the head of cardiology at Sydney University suggests that we should not give up on HDL modification just yet. The editorial suggests that there is some evidence that HDL may be genuinely protective for cardiovascular disease through mechanisms that include the removal of cholesterol from cells involved in the early stages of atherosclerosis (foam cells), immune modulation, and amelioration of diabetes.

However, even if HDL is genuinely protective for cardiovascular disease, that does not mean that something that raises HDL levels will automatically be beneficial for health: if arsenic and cyanide were found to boost HDL levels, that would not be an argument for taking arsenic and cyanide each day.

While the author of the editorial may not want to give up on HDL as a potential marker for cardiovascular disease and a target for therapy, he does concede that: “…it probably is time to abandon our assumption that fibrates, niacin, or CETP inhibitors will improve clinical outcomes in contemporary populations taking statins simply because they have favourable effects on surrogate lipoprotein biomarkers.”

This is a key point: we cannot judge health effects of pharmaceutical agents on their effect on so-called surrogate markers such a cholesterol levels. The only important thing is their effect on overall health. What a shame, then, that we still have regulatory agencies like the Food and Drug Administration in the US and the National Institute for Health and Care Excellence in the UK recommending the use of drugs based solely on their impact on surrogate markers (the drug ezetimibe is a case in point).

It is lamentable that those whose job it is to provide reliable guidance on medical treatments are so stupid and/or corrupt as to recommend doctors prescribe treatments which have no proven benefits and may in fact do considerable harm.

References:

1. Keene D, et al. Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117 411 patients. 2014;349:g4379

2. Kritharides L, et al. Not so “good” cholesterol. BMJ 2014;349:g4664 (Published 18 July 2014)

15 Responses to More evidence that ‘modifying’ cholesterol does not necessarily have broad benefits for health

  1. Anne 1 August 2014 at 4:13 pm #

    If it is protective they should be looking seriously at why some people have higher levels of HDL and some lower levels. I never set about to increase my levels of HDL, but adopting an extremely low carb diet and increasing fats (saturated fats – gasp) my level of HDL has slowly gone up over the years – it’s currently 3.6 ! Nearly half my total cholesterol !

  2. Shaun latouche 1 August 2014 at 8:29 pm #

    Whilst your findings maybe justified in the general context, it does not suggest the evidence for change among those found to be at risk at any level. All the data is down to individual actions and choice and this is not counted for in your research. If not testing was done would the data be different as I’m am sure there are many people both health conscious and otherwise that would act on the results. As a health trainer I have found that the provisions put in place are not necessarily acted apon by everyone at point but will provide anecdotal evidence for justified choices to be made. We ar our own gods bit with some additional information we can become greater with the knowledge of that which we are unaware of.

  3. Jennifer 1 August 2014 at 10:48 pm #

    Dr Briffa, as you said, why are our Regulators recommending Drugs that will do no good but instead inflict a risk for no good outcome at all…

    The very entities charged with protecting the Public are doing the opposite. Why are we not surprised?

  4. Lorna 2 August 2014 at 7:51 am #

    Both articles this week expose the same underlying denial of research and patient experience. I wish I could understand why governments would rather waste money than re-think strategies for health and, importantly, happiness. Taking a drug based on doubtful medical research then having to take more drugs to alleviate side-effects is as crazy as many of the ‘cures’ in medieval medicine.

  5. Maureen Berry 2 August 2014 at 10:11 am #

    The problem is that the whole medical profession have been giving so much bad advice for so long that to ‘come clean’on everything will result in a complete loss of confidence in the medical professionals, the health authorities, successive governments. Where would it end?

    Err, actually……

    Salt is not bad for you.
    Your diet should not be based on carbohydrates.
    Saturated fat is healthy.
    Omega 6 in excess is unhealthy.
    Dr Atkins was right all along.
    Statins won’t effect your mortality, but may alter the ’cause of death’ on your death certificate to something you’d like less than heart disease.
    Diabetics should not have a diet with a portion of carbohydrate at every meal.
    Fruit is ‘nature’s candy’ and other than berries should be eaten for treats only and never juiced.
    There have never been clinical trials based on the ‘polypharmacy’ – multiple cocktails of drugs that virtually all over 60s are exposed to, so we have no idea what the consequences of taking them are.
    Your doctor isn’t allowed to think or research any more, he is only allowed to ‘follow NICE guidelines’ and tick boxes. He’s not even allowed to listen to the ‘success stories’ of his patients.

    I could go on and on and on!

    • Stephen Rhodes 2 August 2014 at 3:15 pm #

      Can we have a recommend/ditto button on your site please John?

      • helen 4 August 2014 at 3:25 am #

        I would like to “like” that post by Maureen Berry too :)

    • M. Cawdery 4 August 2014 at 10:07 am #

      “Your doctor isn’t allowed to think or research any more, he is only allowed to ‘follow NICE guidelines’ and tick boxes. He’s not even allowed to listen to the ‘success stories’ of his patients.”

      “guidelines” – NO!

      To the working doctor (GPs, consultants) they are DIRECTIVES that must be followed because of the fear of legal suit or charges of negligence.

      The term “guideline” is simply to protect the authors!

    • Wendy Haylett 4 August 2014 at 11:50 am #

      Amen to Maureen’s post, as well!

  6. Shaun latouche 2 August 2014 at 5:08 pm #

    Is it not true also that the cost of prescribing drugs is cheaper than the cost of education and training of Heath professionals who have little time to recommend and research data. Also with the recommendations and profit from pharmaceutical companies being the driving force there is little in the way of helpful positive advice for adequate dietary changes in a persons lifestyle to make a difference. Giving a leaflet to someone who needs to make some changed is not a valid or effective method of effective advice.

  7. Dave 3 August 2014 at 12:21 am #

    I’ve read recently that all the prescription forms of niacin don’t work to reduce CHD while plain niacin with the flush increases survival rates by 11%. This last item is the statistic that patients actually want to have! All the prescription forms are just complications serving drug companies and doctors.

  8. M. Cawdery 4 August 2014 at 9:54 am #

    These two books may interest your readers. Both authors (de Lorgeril and Sinatra) are eminent cardiologists in France and the US and are a damning response to the cholesterol-heart hypothesis

    English edition to de Lorgeril, Michel (2014-03-05). Cholesterol and statins: Sham science and bad medicine (Kindle Location 180). Thierry Souccar Publishing. Kindle Edition.

    Sinatra, Stephen; Bowden, Jonny (2012-10-15). The Great Cholesterol Myth: Why Lowering Your Cholesterol Won’t Prevent Heart Disease-and the Statin-Free Plan That Will (p. 9). Creative Publishing International. Kindle Edition.

  9. Z.M. 4 August 2014 at 6:03 pm #

    Once again confirming that the only useful cholesterol lowering treatment is statins, though statins suck at lowering mortality outcomes in the majority of populations.

    Their discussion on LDL was interesting (http://www.bmj.com/content/349/bmj.g4379):

    “Equally an over-simplistic hypothesis for low density lipoprotein could also be considered doubtful. Only one class of agents, the statins, has a large effect on low density lipoprotein cholesterol levels and provides a large reduction in events. With statin treatment in place, no incremental manipulation of cholesterol, low density lipoprotein, or high density lipoprotein levels with a non-statin agent has been found to prevent events so far.

    Higher strength statin regimens do reduce events further in secondary prevention,49 but this is not proof that the accompanying lower low density lipoprotein level is the mechanism of benefit. The multiple effects of statins might be correlated in intensity across drug and dose. If so, effects on lipids and effects on cardiovascular events would be correlated, without the lipid reduction being the cause for the event reduction.

    Notably, fine grained temporal analysis shows reduction in events from use of statins long before the plausible time at which lower lipid levels could mediate slower accumulation of atheroma and thereby could have had an effect.50 Whether the decrease in low density lipoprotein cholesterol level is the principal mechanism for the reduction of acute events by statins is, therefore, unknown.”

  10. Fiona 5 August 2014 at 2:08 pm #

    Maureen Berry could add to her list that we are not all the same size: do I, at 5’2″ and slim, really need as much of a drug as a large 6′ plusser? Fortunately the only regular medication I need is for asthma, but nowhere does the literature suggest that I adjust my dosage according to my size. I’ve never read that, if I’m small, I should take less paracetamol, for instance, unless I’m a child.

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