Medical Statin therapy for healthy people with high cholesterol?

  1. bohm2

    bohm2 817
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    I thought this was interesting commentary in a fairly recent issue of JAMA arguing for the 2 different viewpoints. To prescrtibe or not to prescribe statins for healthy people with high cholesterol?

    Healthy Men Should Not Take Statins

    Statin Therapy for Healthy Men Identified as “Increased Risk”
    Last edited: Jul 17, 2012
  2. jcsd
  3. I suppose you would also have individualize base on a person's BMI, assuming they dont have any risk factors which the people in the article were.
  4. bohm2

    bohm2 817
    Gold Member

    So are you saying that statins should be recommended even for primary prevention when cholesterol is elevated (but without documented coronary heart disease) but only when BMI is high? But if BMI is not high, one shouldn't recommend statins in such patients?
  5. bohm2

    bohm2 817
    Gold Member

    This recent meta-analysis is interesting because it suggests that statins may not even be effective (at least with respect to increasing longevity) in women with coronary heart disease (e.g. secondary prevention):
    Statin Therapy in the Prevention of Recurrent Cardiovascular Events-A Sex-Based Meta-analysis

    So basically, if I'm understanding these studies, then:
    1. statins aren't likely to prolong life in women with/without a history of coronary heart disease
    2. statins are not likely to prolong life in men without coronary heart disease

    So, the only group that appears to derive benefits are men with history of coronary heart disease.
    Last edited: Jul 30, 2012
  6. Monique

    Monique 4,445
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    Isn't it more important to figure out why the healthy individuals are having a high cholesterol and tackle the problem at the root?
  7. bohm2

    bohm2 817
    Gold Member

    That would be a good approach assuming that cholesterol (or at least the small, dense LDL part acording to some studies) is the problem, particularly for men and it isn't something else correlated/confounding. Kind of like fever and infections. It's the bugs that is the problem, not the fever unless fever gets exceptionally high. Thus, if you get rid of the bugs, you get rid of the problem. Anti-fever meds are not getting at the heart of the problem. Some have suggested that cholesterol may be like that and even questioned the "LDL cholesterol drives atherosclerosis" model but such views are in the minority. For an interesting paper on this critical view see:

    The mainstream hypothesis that LDL cholesterol drives atherosclerosis may have been falsified by non-invasive imaging of coronary artery plaque burden and progression
  8. Monique

    Monique 4,445
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    Well, I think using statins to lower cholesterol is metaphorically lowering the "fever" thus not tackling the real problem. My question would be: why is the cholesterol high, poor diet or other factors?

    I also heard that the "bad" LDL hypothesis has been taken into doubt, how accepted is that position?
  9. bohm2

    bohm2 817
    Gold Member

    Genetics and diet determine cholesterol level. As far as I know every major professional health organization supports the LDL hypothesis and recommends some type of treatment based on reaching certain LDL target but type of therapy varies depending on cardiovascular risk potential.
    For instance, the Canadian guidelines that doctors, pharmacists, etc. use (See p. 575 for the summary):

    Canadian Cholesterol Guidelines 2009: Summary of recommendations

    Having said that, there are some health professionals who question some of these guidelines. The most vocal group are the The International Network of Cholesterol Skeptics but again, they are still in the minority. Some have even argued that some of statin's beneficial effects in some patients may be due to anti-inflammatory properties?
  10. Progression of atherosclerosis (and how such progression is measured) and the correlation of serum LDL cholesterol levels with fatal myocardial infarction (MI or heart attacks) are two different questions. As was mentioned, the anti-inflammatory and anti-thrombotic effects of statins may play a role. Abnormal levels of other lipid fractions as well as high serum triglyceride levels are also considered risk factors for fatal MI. Inflammation associated with the rupture of the coronary arterial (endothelial) lining by the underlying atheroma seems to be the precipitating event in the case of MIs, at least according to some studies. This article summarizes situation as of 2002. This is not a new idea.
    Last edited: Jul 31, 2012
  11. bohm2

    bohm2 817
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    The author of that article (Uffe Ravnskov) is or was the spokesman for The International Network of Cholesterol Skeptics (THINCS), I mentioned above. Most experts in the field do not interpret the balance of studies in the same way as that organization; nevertheless, many have questioned the need for using statins in so many individuals especially given the small benefits in all-cause mortality outcomes.
  12. There's nothing wrong with a healthy level of skepticism. The fact is, the science, as judged by regulatory agencies, only justifies the use of statins for secondary prevention of fatal MI (that is in MI survivors) afaik. Any other use of statins, such as in primary prevention, would be considered "off label". The effect of statin therapy on serum LDL cholesterol levels or other lipid fractions is not the critical end point.

    EDIT: One statin (rosuvastatin) has been approved for the primary prevention of MI, stroke, cardiovascular related death and other outcomes in patients who have have certain risk factors for cardiovascular disease.
    Last edited: Aug 1, 2012
  13. the people who have hereditary hyper lipidemia still benefit from statins
  14. Diet and exercise ARE still first line therapy before any statins are recommended in most cases. Only if the individual still maintains a high LDL above the threshold after a certain period of time despite diet and exercise, are then recommended for drug therapy
    Last edited by a moderator: Sep 10, 2012
  15. By definition of "healthy" there is nothing wrong with a "healthy" dose of skepticism, but empirically it is just about always the case that people who label themselves with that word, as did that cholesterol "skeptic", are wrong and seriously unreasonable. I'd challenge anyone to come up with more than one counter-example to my claim. (I do not want to call my self a skeptic about skeptics, though!)

    I also note that after telling us that skepticism can be healthy, you unskeptically post some official guidelines. Guidelines are merely opinions.

    The relationship between LDL cholesterol and heart disease is clearly causal. The correlation between LDL and heart disease is very strong. And it is biologically plausible. A correlation between wearing red socks and heart disease is less plausible because red socks are not found lining the coronary arteries. And regardless of the reason for the elevated LDL any group with elevated LDL has increased heart disease risk.

    People with Familial Hypercholesterimia (FH) lack a full set cholesterol receptors in their livers leading to very elevated cholesterol lervels, and very high risk of heart attack. People with Apo E2 have lower cholesterol levels than average and people with Apo E4 have higher levels, and the heart attack risk is just about exactly numerically explained by the cholesterol levels. The mechanism for Apo E affecting cholesterol is quite different from FH, yet we see the same cholesterol dependence on heart attack risk. Indeed, the reason why Apo E 2 reduces LDL is because there is a defect in the conversion of triglyceride carriers to LDL. And so despite elevated triglycerides people with Apo E2 have lower heart attack rates. And the relationship is even stronger. People with two Apo E2 genes can sometimes develop a cholesterol abnormality (hyperlipoproteinemia type III ) and those people are then, unlike other people with Apo E2 at increased risk of heart disease. And people with high LDL due to diet are at increased risk of heart disease. If it was not LDL directly causing heart disease you would not see the relationship among groups having increased LDL for so many different reasons.

    And just about any method to lower LDL decreases the risk of heart disease--diet, most or all medications, and in the case of people with FH, actually sending their blood through devices to remove cholesterol. Again the diversity argues that the LDL relationship is causal.
  16. No. Guidelines for the use of prescription drugs are based on data, or the lack of data, from randomized clinical trials.

    I challenge you to post a link to a qualified source that says that statistical correlations can establish causality. We can interpret strong associations as possibly causal to some high probability but no responsible scientist would say that a statistical association establishes causality. Do you know what a confounding variable is? Randomization helps control confounding, but most of the data in risk analysis comes from prospective and retrospective observational studies.

    The topic is statin therapy for healthy people with high cholesterol. Do you consider people with FH healthy? No one is questioning the fact that statins lower LDL-C. The question is: Are you treating the patient or the laboratory value? Besides, I've not found any evidence that lowering LDL-C in FH significantly improves survival. Perhaps you could find something?

    I believe elevated LDL-C is a predisposing factor for MI, but is it a necessary cause? If so, how do you explain MI's in people with normal or low LDL-C? They are not uncommon. Are you aware of the Jupiter trial? You should be if you are making these kinds of arguments in these forums. The rules require that you post links to qualified sources to back up what you say. Just posting your opinions is only allowed in the General Discussion forums.
    Last edited: Sep 5, 2012
  17. bohm2

    bohm2 817
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    Some might this summary of lipid trials interesting. Note:

    1. Primary vs Secondary prevention
    2. All-cause mortality when comparing drug vs placebo
    3. The # of people and # of years of treatment needed to save 1 life (and it's not clear for how much longer that person may survive?)

    And also keep in mind that published studies tend to over-represent positive trials (e.g. publication bias) as pointed out in many reviews. I think one can make a good argument that such funds can be used elsewhere for greater health benefits.

    All-cause mortality outcomes from major lipid trials

    The source is Rxfiles, a summary used by Canadian doctors and pharmacists to help guide drug therapy decisions.
  18. SW VandeCarr writes the following and then provides us with a link to a study in a prominent medical:

    Yes, I can find something--the very article you linked! You very seriously misundersood it. It actually says the opposite of what you thought it said. It did not say that statins were not beneficial in people with FH. It says they are. What it said that confused you was that adding a second drug gave no additional benefits over the benefits statins gave.

    I would very strongly urge people interested in this discussion to read the article SW VandeCarr adduced, and see what it actually said. Here it is again:


    I would explain the situation as beiong analogous to the situation whereby some people who were not driving drunk die in car crashes. Drunk driving makes one more likely to die in a car crash, and elevated cholesterol makes one more likely to die from a heart attack. In both cases the correlation is causal.

    I'm not sure what you mean by "predisposing factor"--I was under the impression that previously you cited approvingly that skeptic group which claimed elevated cholesterol does not increase the risk of heart attacks.

    Responding to me saying that guidelines are opinions, SW VandeCarr responds:

    Obviously the guidelineswes have some relationship to the data, but that does not make them not be opinions. They are the opinions of certain people about the data. Indeed, all opinions have some factual motivation (unless they are really unreasonable), but opinions are still opinions.

    But what I find puzzling is that you keep using "appeal to authority" while saying how proud you are to be a "skeptic" and while taking a view on cholesterol that respected authorities strongly reject. The group you cite "The International Network of Cholesterol Skeptics" is not considered a mainstrean scientific group, while the American Heart Association, the National Institutes of Health and the Surgeon General, all of which disagree with you, are considered authorities. It is fine for you to have a non-standard view if you can argue it with facts and logic, but it makes no sense to use appeal to authority when you are taking a position at odds with authority.

    Indeed I do. And in my vey first post in this thread I, in great detail explained how we know that the correlation is not due to confounding, so perhaps you should ask yourself the question you just asked me. I will summarize it for you.

    If there was just one way that high cholesterol was linked to increased risk of heart attack, then confounding should be a concern. So, for example, if studies found that people who ate red meat had higher cholesterol and higher rates of heart attack then we could wonder if maybe, for example, the real culprit was iron in red meat. But there are many disparate unrelated modes of getting cholesterol--diet, genetic deficiency of cholesterol receptors to remove cholesterol from the blood, genetic predisposition to have increased conversion of triglycerides to LDL cholesterol, and all of them lead to increased risk of heart attack. Furthermore, there are many ways to lower cholesterol--diet, statins, blood filtration, and almost all lead to lower rates of heart attack. So it is not some confounding that is going on--the risk is fundamentally from the cholesterol itself.

    It seems that you might be thinking that a correlation must be strong in order for it to be causal. That is not mathematically correct. While, everything else being equal, a stronger correlation argues more strongly for causation, it is not always necessary.

    Suppose one flipped a coin "in a fair way" (i.e. the flipper has set things up correctly, but the coin itself might be defective) and got heads 55 percent of the time. There is only a weak correlation between flipping and getting a head. But it this was over, let's say 10^90 fair coin flips the effect would clearly be causal--we could determine that the coin itself was not fair.

    I find this very strange from someone who posts stuff from that "International Network of Cholesterol Skeptics" group. I don't know what you want from me--I've posted quite a bit about the science. Do you want me to cite authorities--sometimes you engage in "appeal to authority" but sometimes you tell us you are a skeptic and you post views clearly at odds with mainstream medicine. So what do you want?

    But most puzzling is that in a post that was rude, condescending, and now threatening, you claim I am breaking some message board rule. You need to check the rules for yourself.
    Last edited by a moderator: Sep 10, 2012
  19. Where does the article say anything about survival? The end point was intima-media thickness of the coronary arteries; the measurement of which has been challenged by the "cholesterol skeptics". It's in the Ravnsknov Oxford Journals paper I posted earlier. If the second drug (ezetimibe) were effective, it would have supported (not proved) the hypothesis that cholesterol levels alone are causal.

    I don't consider myself a "cholesterol skeptic". However, I do think they make some good points. Atherosclerosis and its relationship to various presentations of cardiovascular disease (CVD) is complex. It's not a simple matter of blood levels of LDL-C or even the (total cholesterol)/ (HDL-C) ratio. Some of the papers I linked to clearly make this point. C Reactive Protein (CRP) appears to be an independent risk factor and there may be other independent risk factors.

    Your use of the word "causal" is IMO inappropriate. Causality is established by experiments. Our ability to do medical experiments involving human beings is obviously limited by ethical considerations. In a true experiment you can more effectively isolate the variables of interest and manipulate them. The most rigorous medical experiment allowed for these kinds of questions is the randomized double blinded clinical trial. It reduces but does not eliminate confounding and the only variable you can manipulate is the treatment. The results are determined on statistical grounds based on normal theory. I'm not criticizing the methodology. This is how I once earned my living, but I do recognize the limitations.

    Causality is usually described in terms of "sufficient cause", "necessary cause", and "necessary and sufficient cause". These terms might be applicable to infectious diseases where the infecting organism or agent is the necessary cause (but usually not a sufficient cause) for the relevant disease. I would again challenge you to find a paper in a reputable refereed journal that uses these terms in reference to the present subject. So far you have not supported your arguments regarding your use of the term "causal" as required in these forums.

    EDIT: I also find your characterization that regulatory agencies (specifically the US FDA) operate according to their opinions to be unfounded. Major decisions like product approval and labeling are a very public affair involving experts from the academic community and the pharmaceutical companies. Even if the regulators have opinions, there are sufficient checks on any arbitrary and capricious actions on their part. I know the process very well. I would suggest you don't.

    Do you consider the articles I linked in refereed journals to be at odds with mainstream medicine? Science is not (or should not be) dogmatic. As I said, I don't subscribe to the complete skeptical thesis. Cholesterol is a factor in CVD and statins are effective, but possibly not only because they lower LDL-C, but also apparently because they lower CRP (Jupiter Trial) and may also have anti-thrombotic and anti-infammatory effects as suggested in linked articles. This, however, remains to be studied.

    Apparently you've translated my "healthy dose of skepticism" into some kind of irrational extreme position. I don't know if that's deliberate or not.

    The rules say you must support your claims in the science forums by referencing valid sources.

    Last edited by a moderator: Sep 10, 2012
  20. bohm2

    bohm2 817
    Gold Member

    Not sure if this study was mentioned but there's also the ARBITER 6-HALTS trial. In that trial ezetimibe produced greater reductions in LDL cholesterol (so-called “bad” cholesterol) but resulted in no overall improvement in carotid intima-media thickness. In fact, individual results suggested greater thickening with greater LDL reductions. The use of etezimibe was also accompanied by a higher number of heart attacks and deaths:
    Settings Extended-Release Niacin or Ezetimibe and Carotid Intima-Media Thickness

    The ARBITER 6-HALTS Trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6–HDL and LDL Treatment Strategies in Atherosclerosis)
    Last edited: Sep 7, 2012
  21. Since you posted 6 in a row without waiting for a response , I'll respond at my leisure to the extent I feel it justifies a response. This post indicates a poor example of scientific reasoning. All the factors you named (and many more), for the sake of this discussion, are considered to be "risk factors" for high serum cholesterol, and in particular LDL-C. Some relationships were discovered in randomized trials were it's presumed that confounding is adequately controlled. However, most of these relationships were discovered in observational studies where potential confounding factors must be identified and controlled. The best of them use very sophisticated multivariate regression models, but for many reasons which I won't list here, they can never justify the confidence one might place in a large well managed randomized trial. Nevertheless, there's little controversy regarding the amount of certain kinds of fats in a diet contribute to high serum cholesterol levels, particularly LDL-D and triglycerides. Other factors such as genetics, and exercise level are considered risk factors for elevated cholesterol (including the total cholesterol-HDL-C ratio.)

    To keep things simple, I'll concentrate on just one value, LDL-C. Everything that I talked about above are considered explanatory variables contributing to this one value. This value is considered to be a risk factor for atherosclerosis. Now, we have to make the connection between atherosclerosis and the specific CVD outcomes (heart attack, stroke, etc). Here, we now know that high sensitivity C-reactive protein (hsCRP) is a major independent risk factor for MI (heart attack) through inflammation and clot formation. Your characterization that, say eating red meat causes heart attacks is a misleading and unscientific oversimplification. It may true, but "may be" is not the way you support the claim of strict causality. I will agree that a diet very high in red meat increases your risk for a heart attack if your LDL-C is elevated. I don't agree that we can say this will be the cause of your next heart attack.

    Causality is an empirical concept. It's not defined in mathematics or logic. Philosophers have debated about what it really means. I prefer the simple but powerful concepts of "sufficient cause" and "necessary cause". Here the concept of LD(x)50 and LD(x)100 (lethal dose of x for a percent of a population)is useful. At LD(x)100, every individual in the population is dead. In a controlled experiment, we can say that x at D is a sufficient cause of the deaths (ie D(x)=LD(x)100) if all the subjects are dead and all or almost all the controls are alive. Presumably, the subjects in such an experiment are not human beings.

    I believe saying x causes y is meaningless unless you state it in terms of a necessary and/or sufficient cause.
    Last edited: Sep 10, 2012
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