18 Cholesterol Confusion 1 Primordial Prevention
By now I hope you have at least seen my Pesky Facts video so you know why high cholesterol is so closely linked to heart disease. This graphic is just here to remind you of that before we dive into all this cholesterol confusion. You are looking at a visual for the relationship between blood cholesterol and deaths from heart disease using data from two different studies, one of which was quite large. This graph tells you all you really need to know about cholesterol. There is a lot that can be confusing about this topic, but for all practical considerations, the lipid hypothesis is pretty simple, as you can see. If cholesterol somehow weren’t really related to heart disease, we would have a tough time trying to explain the relationship you are looking at in another way.
With that understood, lets get acquainted with what I consider to be the biggest source of confusion about cholesterol. You’ll notice as you watch the videos in this portion of this series that all the concepts we’ll be examining are closely related. I think the misunderstanding that is the subject of this video is hard to separate from most of the others.
This article by Allan Sniderman and colleagues argues that we should think in terms of a “causal exposure model of vascular disease.” Sniderman distinguishes this model from the risk factor model, which is how most people think of heart disease today. The risk factor model has worked but it hasn’t worked well enough. Sniderman says that the problem with it is that it results in the initiation of therapy to combat heart disease too late in the disease process. Treating risk factors late in life is a bit like closing the barn door after the horse has bolted. There is only so much that can be accomplished with drugs after a certain point.
We shouldn’t just conceptualize the heart disease process in terms of 10-year risk ratios. Sniderman and colleagues argue that we need to think more about reducing the cumulative time that a risk factor like high LDL is present in each of us.
Age is an important risk factor for adverse events because age represents all the time that a harmful condition like high LDL has had to do its damage. If we think of heart disease this way, it then makes sense for us to try to get to work on prevention efforts much earlier in life.
Heart disease eventually catches up with most of us. It may not happen in the next ten years, but that doesn’t mean that heart disease isn’t always progressing toward a very bad event. Just because an adverse event like a heart attack may not be likely in the next ten years for a patient, that doesn’t mean that that patient isn’t moving ever closer to that event every day.
The idea that we should take steps very early in life to prevent heart disease is called primordial prevention. The promotion of the primordial prevention approach is one of the main objectives of my Primitive Nutrition project. I am convinced that a healthy lifestyle maintained over the long term is the cheapest, safest, and most effective way to reduce the suffering caused by heart disease and other major non-communicable diseases. Primordial prevention is the best way for our society to lower our health care costs and improve our health outcomes at the same time.
Sniderman and his colleagues correctly noted that the primordial prevention approach requires us to be willing to act on the best research we have rather than perfect research since there will never be a controlled study long enough and controlled enough to clearly demonstrate the effectiveness of primordial prevention.
That being said, there is a lot of research out there that should make their causal exposure model easy for us to accept. This article looked at the health of participants in the Framingham project over a 50-year time span. It was found that those with optimal risk factors over that long stretch of time had a dramatically lower risk of suffering an adverse event than those people who exhibited two or more risk factors.
As you can see, cholesterol was one of the risk factors that was considered here. For both men and women, total cholesterol over 240, represented by the solid line, correlated to a higher incidence of cardiovascular disease for all ages over 50. This is the cholesterol story in a nutshell.
This study conducted in Helsinki looked at a 39-year time span. Please notice, cholesterol deniers, this looked at total mortality, not just cardiovascular mortality. If you are genuinely inclined to assess the lipid hypothesis based on total mortality, you should understand that that angle definitely supports the idea of keeping cholesterol levels down. Those with low cholesterol at midlife had better survival and better physical function.
These authors understood the causal exposure model. They concurred with Sniderman’s point that cholesterol-lowering drugs given late in life can only have limited impact.
These same authors also published a similar paper after 46 years of follow-up. They said, “a strong and graded relation was found between the cholesterol level and total mortality.” Cholesterol levels after the year 2000, when these people were at their oldest, were not predictive. People with lower mid-life cholesterol were generally more physically able as well.
We can also see the causal exposure model in action if we look at the effects of genetic polymorphisms that keep LDL cholesterol low. Brian Ference led a study that looked at nine such polymorphisms to see how they affected heart disease risk.
It is quite useful to consider the effects of genetic polymorphisms in discussing the subject of cholesterol and heart disease. The idea Ference and others rely upon in this type of study is called Mendelian randomization. This paragraph explains why naturally distributed polymorphisms are studied as if they were treatments. This method is the best way to look at lifetime risk given the impracticality of doing well-controlled lifetime trials of diets and drugs. Those trials will never happen and that’s just fine, regardless of what Gary Taubes is telling his gullible wealthy donors to his nonprofit.
Ference found that those with lower LDL levels over the long haul have a much lower risk of suffering a heart disease event. Other studies before this one used this same approach on a smaller scale and arrived at the same conclusion.
The best known of the LDL-lowering polymorphisms is PCSK9. Over a 15-year interval, those with mutations to PCSK9 that result in lower LDL cholesterol had a 47% reduction in risk. The authors stated that moderate lifelong reductions in plasma LDL cholesterol are associated with substantial reductions in the incidence of coronary events. Findings like this explain why we will see new drugs soon that target PCSK9.
At the other end of the story about genetics and LDL is familial hypercholesterolemia, or dangerous genetically raised cholesterol. Those with the worst types of FH have 6- to 10-fold increases in LDL. Consequently, they can have heart attacks during childhood.
The research using Mendelian randomization has also deflated the common belief that high HDL, which is the good cholesterol, is protective against heart disease all by itself. This study published in 2011 found that while genetically lowered LDL prevented heart disease events, genetically raised HDL did not.
A study in The Lancet earlier in 2012 which told us the same thing about HDL received a lot of news coverage. Remember that low carbers have used the HDL rationale to justify their approach. Robert Atkins was especially invested in low carb’s effects on HDL. They were all way off, as even low-carb lipidologist Thomas Dayspring will tell you. HDL is a very complicated lipoprotein. I doubt it will ever supplant LDL as the main target of treatment.
Here is an especially interesting study of genetic polymorphisms that was conducted in Copenhagen. By comparing the health outcomes of people with genetically low LDL cholesterol, these researchers were able to dispel that false claim by the cholesterol deniers that low cholesterol will give you cancer. That’s yet another low carb lie that can’t survive contact with serious scientific scrutiny.
The Atkins people really have no clue about concepts like primordial prevention and causal exposure. Here you can see their ignorance in action. The Atkins Foundation put out a press release to dispute a study that linked the increased popularity of low-carb diets to worsened cardiovascular risk factors, especially high cholesterol. Their smartest proponent, Stephen Phinney, said:
“This study does not take into account other variables or factors taking place in the Swedish demographic in this time period… For one, they do not take into consideration the effect of age on the population. The Swedish population is rapidly aging, and this is most notable in the northern part of the country where this study was done and I did not see where they corrected their data on weight or cholesterol for change in mean age. And most importantly, anyone attempting to assess health risk by change in total cholesterol does not appreciate the science of the last 30 years. Particularly notable is the lack of information on serum HDL cholesterol and triglycerides.”
So you see the news hasn’t sunk in for Phinney yet that the HDL sales pitch isn’t going anywhere anymore. He also is apparently in denial about the effects of fatty animal foods on LDL. As you know by now if you’ve watched my videos up to this point, many controlled trials in metabolic wards have conclusively demonstrated that these foods raise LDL and total cholesterol. I am at a loss to think of a way Phinney could dispute that. I wonder if there is any researcher out there who demonstrated that fatty animal foods raise cholesterol whom he would trust. Maybe he would at least listen to someone he trusts. I don’t know Stephen Phinney but I’ll bet I can name the researcher he trusts the most.
Himself. Stephen Phinney actually wrote a paper showing that fatty animal foods raise cholesterol. Just try to get inside the head of a man who would argue that low-carb diets don’t raise cholesterol who also did a study of his own using a low-carb diet that produced a very dramatic increase in cholesterol. Upon what basis would he reject his own research, I wonder? It’s almost 30 years old. Is that the problem? Maybe he thinks humans have changed in some fundamental way in the last 30 years. How else can he argue with his own research? Phinney wrote that this increase in cholesterol among the athletes he worked with wasn’t worrisome because their total cholesterol never got out of range. Why didn’t their numbers go any higher than this? Because Phinney ended the study!
Look at how those numbers just kept going up. Why would he think they would top out at the exact moment that he ended the study?
He wrote that his participants’ elevation in total cholesterol when on a ketogenic diet appeared sustained. Can you believe he so blatantly contradicted himself? These guys are amazing.
Phinney’s quote brings me to an important yet often overlooked aspect of lifetime exposure to high-fat diets and high LDL. When Phinney says that the Swedish population had gotten older and that those study authors didn’t correct for age, he doesn’t seem to realize that age would actually tend to obscure the effects of high-fat diets over time. Cholesterol doesn’t necessarily just go up and up and up just like in his study, all the way until you die.
Imagine something for me. If you decided to start reading a novel in the last chapter, skipping everything that happened in the book before that, would you expect to understand what was happening in the story very well? I’m guessing you’d understand you were missing out on some important information. You wouldn’t try to pretend otherwise. Those chapters are right there, attached to the book, and you would know you hadn’t read them.
Yet it seems many people think all they need to know about the cholesterol story can be learned by studying older people. They seem to think the whole history of heart disease in the individual just starts to be written in the later part of life when the dangerous effects of heart disease really start kicking in. The clearest and most egregious examples of this faulty logic are those bizarre arguments from the confusionists about atherosclerosis at autopsy that we reviewed in video 6 of this series.
Stephen Phinney should know that in wealthy populations that eat a lot of animal foods, cholesterol is artificially raised until past midlife, when it starts to come back down as they get sick and old. That’s what you see in those top few lines. It is only in populations with low cholesterol levels over their lifetimes that cholesterol doesn’t plummet in the years prior to death. Their cholesterol doesn’t fall because it was never artificially raised in the first place. Once again, the reason age is a risk factor is because older people have had more time for their high cholesterol to hurt them. Only by maintaining low lifetime levels of cholesterol can this risk be minimized.
That big decline in cholesterol with physical decline has been observed a lot over the years. It is caused when comorbidities and failing health produce a drag on cholesterol levels. You can see here that this doctor all the way back in 1933 noticed that low cholesterol could be connected to infectious disease.
Here in 1960 you can see the big decline over time in this study comparing monks. This pattern was observed quite long ago but Steven Phinney apparently doesn’t know about it yet.
Here is a paper from 1973 which noted a sharp fall in cholesterol for men over the age of 60. What do you think caused this, Dr Phinney? Do men in their 60s all of a sudden decide to become vegans? Or does this drop happen because they are basically collapsing as they approach the finish line?
That study I showed you looking at cholesterol levels over a 39-year time period included a great graphic making this point visually. Notice how those with low cholesterol early in life don’t have far to fall at the end of life. Meanwhile, those with high cholesterol experience dramatic declines.
These days, the drop in cholesterol at the end of life might also be caused by the use of cholesterol-lowering drugs. Remember, Sniderman’s point in that causal exposure article was that drug interventions at the end of life can only do so much, but this is still the way high cholesterol is addressed by many in the medical profession today.
Interestingly, some studies using data from autopsies have shown that at the end of life, the progression of atherosclerosis tends to slow down. It may be that even if cholesterol is going down for a bad reason like failing health, lower cholesterol means less atherosclerosis. Unfortunately, plaques become less stable with age, so this benefit would occur too late to benefit anyone.
This understanding of how cholesterol works over time will help you to see through most of the dumb ploys of the cholesterol deniers. I can see how these patterns might be missed by someone with sincere good intentions. You have to know this information to understand what you are seeing in cholesterol numbers at the population level. There is another source of confusion that I have a hard time believing is the result of a simple misunderstanding, yet it is incredibly commonly used by confusionists. I’ll explain “the cause of heart disease” next.