Does cholesterol cause heart disease? New study says no

Generic Pack of Statins

Does LDL cause heart disease? The debate rages on, and now we have another publication questioning the role of LDL as the primary cause of heart attacks and strokes.

A new study published in Expert Review of Clinical Pharmacology reviewed data from over 1 million individuals and concluded that LDL does not cause heart disease. This is in direct contradiction to recent publication European Society of Cardiology stating that LDL does directly cause heart disease.

Irish Times: No evidence that high cholesterol causes heart disease

Who is correct, and how do we know what is best for our long-term health?

It’s complicated. That’s the answer nobody wants.

Doctors, health systems and drug companies want a simple answer with a simple solution. They all have their own reasons, but the goal is the same. Don’t confuse patients. Keep the narrative one of good and bad and have a simple solution (statin prescription).

And let’s not forget the rest of us individuals. We don’t want confusion either. We want to know that we are doing the right thing to improve our health.

But what does the literature support? Again, it’s complicated.

Question #1– How many “exceptions” does it take to negate an argument? Accepting for a moment that there is evidence to support that LDL causes heart disease (more on this later), there also happen to be numerous exceptions.

  1. It is taught that individuals with familial hypercholesterolemia, a genetic disease resulting in markedly high LDL levels at a young age, die young from heart disease. That is true for some, but definitely not all. In fact, there is some evidence that those who don’t die from heart disease actually live longer than their age-matched cohorts. Why don’t they all uniformly die young? There are clearly other factors involved beyond LDL.
  2. Women over age 65 with elevated total and LDL cholesterol live longer. Again, how is this possible if LDL uniformly causes heart disease?
  3. Studies looking at patients admitted with heart attacks show that the majority do not have elevated LDL levels.

Some would argue these three points completely negate LDL’s role in causing heart attacks. Others suggest they are exceptions to the rule.

Question #2– How good is the evidence supporting LDL’s role for causing heart disease? Studies evaluating over 20 million subjects show an association between higher LDL and increased risk of heart disease. For some, that is enough to convict LDL. But does that apply to you as an individual? That is where the strength of evidence breaks down.

  1. Mendelian randomization trials (a fancy name for genetic trials) show that those with genetic mutations resulting in very low LDL have lower risk of heart related deaths. They also show that those with elevated LDL have an increased risk of developing heart disease at a young age. But again, neither of these examples are close to 100%. We also have to realize that most genetic mutations have more than one effect. Could there be something besides the LDL change that impacts our health? Absolutely! The genetic trials, therefore, may not be the best example of “proof” that LDL is the issue.
  2. Drug trials that lower LDL show a small reduced risk for heart attacks. This is likely the most controversial topic. For starters, the vast majority of these trials involve statins which have more than just LDL lowering effects. They also reduce inflammation, they resist blood clot formation, and likely have other effects we don’t know about. How can we say it is all due to the LDL? We can’t. Also, they have an absolute benefit of less than 1% in most studies, a fairly paltry number when considered on an individual basis. Plus there are other issues:
    1. There is the mystery surrounding much of the data. For instance, the CTT is one of the most influential studies to support the claim that we need to lower LDL in most populations. The problem is they have kept their data secretive and therefore it has not been evaluated by an objective third party. There is now a policy that all data has to be made public, but that does not help us for older data.
    2. In addition, there is the influence of pharmaceutical companies. The majority of drug trials are directly sponsored by pharmaceutical companies and the investigators are paid hundreds of thousands of dollars by these companies. Finding a study without a laundry list of conflicts of interest is near impossible.
    3. These trials are designed ahead of time to maximize potential benefit and minimize potential adverse effects. For instance, they frequently have a run-in period where anyone who has side effects from the drug are automatically excluded from the trial. That’s how they can report a 1% side effect rate, because everyone else was excluded from the beginning!
  3. Observational trials link those with higher lipids to an increased risk of heart disease. Hopefully we can all understand the limitations of observational trials. What else were they doing to increase their heart risk? Were they overweight? Hypertensive? Pre-Diabetic? Smokers? Poor exercise habits? All of these are confounding variables that trials cannot completely control for.  In addition, the correlation with heart disease breaks down when controlled for low triglycerides and high HDL (findings commonly seen on a low carb diet)

So, what’s the answer for you as an individual? Do you have to worry that elevated LDL will cause heart disease?

It depends on what else is going on with your health, what your other risk factors are, what your lifestyle is like and so much more. We are indebted to Drs. Sultan, Kendrick et. al. for exposing the other side of the debate and pushing back against the unified voice of our healthcare industry preaching that LDL definitively cause heart disease.

We should all be thankful for the discussion, for the debate, and for the investigation of nuance. Life is not as easy as good and bad or black and white. We need to be comfortable in the shades of grey.

Just know that you don’t have to do it alone. Reputable communities and sources of information like here at DietDoctor.com can serve as a source of education, clarification and inspiration for you on your health journey. We are here to help you. Please let us know what you think about the LDL debate and how we can help clarify the issue better for you.

Thanks for reading,

Bret Scher, MD FACC

The study

Expert Review of Clinical Pharmacology 2018: LDL-C Does Not Cause Cardiovascular Disease: a comprehensive review of current literature

Irish Times: No evidence that high cholesterol causes heart disease

Earlier

“Good health rarely comes out of a medicine bottle”

New study: Keto improves cardiovascular health markers

Heart disease and cholesterol

Keto

17 comments

  1. Peggy Holloway
    What is missing from this otherwise excellent article the physiologic mechanism that would explain exactly how LDL could cause heart disease. It is my understanding that there is no such evidence. For me, physiology and biochemistry outweigh any other discussion.
  2. David
    There is an excellent series of Youtube videos by Professor Ken Sikaris. He is with the Melbourne University Pathology Unit and presents information without trying to persuade one way or the other. In one of those, he suggests that heart attacks and strokes begin with inflammation of the blood vessal or artery wall which then causes an immuno response. Cholesterol is part of the immune response and hence its association with heart disease. So, in the same vein as the article, does cholesterol cause heart attacks no but it may contribute to them.

    I have seen it suggested somewhere that one of the biggest causes of inflammation is the consumption of highly refined grains (bread being one of the worst).

    Incidentally, one side effect of statins is that they help to reduce inflammation and this could be the real reason why there is a 1% improvement in heart attack risk. However, given other issues and unknowns with statins, I won't be going back on them anytime soon.

    Reply: #10
  3. Janet
    My twin sister and I have total cholesterol levels >350mg/dL but have never heard of anyone in my family having heart problems. I have a keto diet (my sister does not) and we have almost the same levels. Familial hypercholesterolemia (FH) is defined as 'a genetic disorder of lipoprotein metabolism characterized by highly elevated plasma total-cholesterol levels with detrimental cardiovascular consequences that commence in childhood'. There must be many, many people with high levels of total cholesterol but no heart disease, we are not unique. The knee-jerk reaction of my doctor to put me on statins despite high HDL levels, very low triglycerides, normal blood pressure, no diabetes in the family etc is probably repeated in doctors surgeries everywhere!

    There is also evidence https://bmjopen.bmj.com/content/6/6/e010401 that high cholesterol is protective in older women (we are 68) 'Conclusions High LDL-C is inversely associated with mortality in most people over 60 years.'
    Needless to say we will not be taking statins.

  4. David
    Read the article " the straight dope on cholesterol" by Dr. Attia. It's an eye opener....the real culprit is LDL-P. People with low tryglecerides and high HDL generally have low LDL-P. Meta data shows cardiovascular vascular events occurs most frequently in patients with high LDL-P and low LDL-C....this is called discordant.
    Reply: #9
  5. Birgit
    Those simplified answers that so many people seem to prefer and therefore doctors prefer to tell their patients have been my greatest enemy throughout my life. As I literally perceive the world differently, from different vision pattern, conscious color perception, range of audible sound frequencies to even different emotional and logical processing, those simplifications did never fit.
    As a consequence, the use of simplifications by anybody makes that "fact" lose credibility at once in my eyes.
  6. Brenda
    I have been low carb for 2 1/2 years now. While my cholesterol was never that bad, the last blood test taken a few weeks ago really surprised me. My total cholesterol is just over 200 (in the red, so to speak) which was lower before the diet change. But my triglecerides and HDL shocked me. While they were never bad, triglicerides have plummeted to 38 and HDL has soared to 114. I don't think they get much better than this.
    Reply: #8
  7. Frank Hummer
    On your point about the fact that genetic mutations sometimes have more than one effect, I have heard that some people with familial hypercholesterolemia have an accompanying mutation that causes high fibrinogen; the ones with high FBN tend to have CVD, the ones without high FBN don't tend to have CVD, and actually tend to live longer.
  8. Frank Hummer
    Yep, this is a classic low-carb profile. I wouldn't worry at all about cholesterol over 200. The HDL/Tg ratio is an important marker for health, and yours is excellent.
  9. Frank Hummer
    I thought I was upvoting your comment, but it looks like I accidentally "reported" it. Sorry! I hop the moderators read my apology.
  10. Frank Hummer
    I've seen some of those videos, and they're really great.
  11. Leslie
    Do you have any information on the role of Lp(a) and associated elevated LDL? Is there increased risk for CV events with the presence of elevated Lp(a) and a strong family history of early MI's and hyperlipidemia, particularly in women?
  12. Ruth
    I have high cholesterol and my doctor wants to put me on statins. I don't want to go on them. My doctor sent me for a CT calcium scan which states I am high risk for heart disease. Are the results of this scan something I should pay more attention to than my cholesterol level?
  13. Yvonne
    Last year my doctor prescribed Statin (Zovar) and blood pressure medication (Acapril). Having researched the current debate about Statins (18 months previously) I was very dubious. I am (just) 58 and have been blessed with what I consider good health. I have always turned to Naturopathic and Oriental healing modalities when needed and only take pharma drugs (short term) for acute conditions, if absolutely essential. But, I decided to 'try' the 'medication'. Within 3 days my legs were not working normally so I quit the blood pressure med (Acapril) to find out which one was causing the problem. By day five I couldn't even walk my dog around the block whereas I would normally hike for about an hour every day! Day 6 ~ I quit the Statin(Zovar) and will never, ever take one again. My final analysis ~ do your own research ~ weigh up the pro's and con's ~ make an informed decision that YOU feel comfortable with. There will always be debate ~ the really great thing is that we have (in the internet) a marvelous platform for sharing information. This is what empowers us all: enabling us take our own health into our own hands. P.S. I binned the medication & never went back to the Doctor. However, I do believe he is doing what he believes is best for his patients. It's the way he was trained, unfortunately. Diet Doctor is a fantastic resource ~ Thank you!
  14. Anees Shah
    There are various causes of high Cholesterol that can lead to a critical heart problems.

    https://everydayscience.blog/what-is-cholesterol/

    Replies: #15, #16
  15. Gentiann
    Really????
    Your information seems so outdated!
    You probably skipped the studies showing the opposite view....
  16. Mia
    I agree with Gentiann's assessment. This is a terrible article. Bumps, loss of appetite? There are no 'symptoms' of high cholesterol that one would be aware of - at least not that I'm aware of.
  17. Janet Love
    In our society the task of prescribing co$tly healing medicine is restricted by law to 'Doctors' of Medicine. As such, we need to re-visit the term "Doctor", derived from the Latin 'docere' = Reaching a high(est) academic standard and fit to teach, make clear, arrange &convey correct knowledge ...
    Somewhere, sometime, the educational role of the medical doctorate has been forgotten, but the internet's ubiquity has stripped away professional secrecy...and we patients are free to pursue the Facts and even educate ourselves, unencumbered by financial (kickbacks) , fraternal (Accepted medical practices) or other conflicts of interest.
    For the first time in the history of Doctor-Patient relationships, we can Ask the Questions AND have insight to the correct answers.
    On the other hand, this same Internet provides a conduit for motivated Physicians to effectively inform, warn, and benefit a the Interested Audience, - and we thank them for that.

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