Does Cholesterol Cause Heart Disease? New Study Says No

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

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