How heart disease works

heart 665186 640Today we're going to look at the mechanics of heart disease; I have only touched on what I believe to be the best way to tackle the problem. I will leave that for another post.
If you have a doctor that is very open, you might be able to give him information like this so he can bring himself up to speed on what is happening with research in this field of medicine from around the globe. I hope doctors will read this and make up their own mind as to the common sense and validity in these words.

The measurement of cholesterol has undergone a dramatic evolution over the past 70 years with technology at the heart of the advance. This information is to give to those that are interested the latest in lipid research.

I was born with a bicuspid aortic heart valve which has been replaced, so I have developed an interest in heart health. I am still continually increasing my knowledge about this subject, which kills more people in western societies than any other disease. In the USA a woman is 7 to 8 times more likely to die from heart disease than she is from breast cancer. Heart disease is the leading cause of death in the USA and 25% of all deaths is attributed to heart disease.

I know that when I visit my cardiologist and he sees my total cholesterol (TC) and LDL cholesterol numbers he almost has a heart attack. This is because the high numbers I have are considered dangerous by most cardiologists and GPs in this country and overseas, but research over that last 10 years has shown that death from heart attacks is a lot more complicated than high LDL cholesterol and TC .

A doctor/researcher by the name of Peter Attia has written some great articles on this subject and I’m going to include a lot of information that has been written and researched by him. Peter earned his M.D. from Stanford University and holds a B.Sc. in mechanical engineering and applied mathematics. Peter trained for five years at the Johns Hopkins Hospital in general surgery, where he was the recipient of several prestigious awards, including resident of the year, and the author of a comprehensive review of general surgery. He also spent two years at NIH as a surgical oncology fellow at the National Cancer Institute where his research focused on immune-based therapies for melanoma. He has since been mentored by some of the most experienced and innovative lipidologists, endocrinologists, gynecologists, sleep physiologists, and longevity scientists in the United States and Canada.

Other material has come from my research and notes I have done over the last 4 years and includes a lot of information from many lipid researchers from around the world, including cardiologists.

When giving advice to their patients, most doctors will say this to you:

1. Heart disease is caused by too much “bad” cholesterol (LDL-C). LDL-C is the amount of cholesterol contained in all LDL particles.
2. LDL-C is one of two cholesterol measures you need to worry about.
3. The other is HDL which should be high and within the suggested range.
4. When ‘Calcium scores’ and ‘CT angiograms’ (CTA) are negative, there is no need to treat the patient.
5. Atherosclerosis is a disease which narrows the pipes (arteries) in the heart.
6. There is no role for preventatively treating young people, except in very rare cases like familial hypercholesterolemia (FH). FH is a disease whereby LDL receptors in the liver are not working correctly and can’t take excess cholesterol away, so cholesterol builds up in the blood and body tissue.

Here are counter arguments:

1. Atherosclerosis is caused by an inflammatory response to cholesterol embedded in artery walls. The cholesterol is delivered by LDL particles and atherosclerosis is better predicted by the number of lipoprotein particles (LDL-P) than by the cholesterol they carry (LDL-C). If VLDL can’t get rid of it’s triglycerides it will make more VLDLs because they need to carry a set amount of cholesterol, and if there’s no room (because they are filled with TGs) it has to make the room by making more VLDLs. This is why low fasting blood TG is a good indication things are ok even though LDLs are high.
2. LDL-C is only one measure and research has shown by itself does not accurately predict cardio vascular events.
3. It seems looking at the latest research that HDL in excess can have inflammatory consequences. As with LDL in appears particle number (HDL-P) is the important marker. All things being equal it seems smaller HDL particles are more protective than large ones.
4. Calcium scores and CT angiograms of exceptional quality (the operative word being exceptional—most are not) are helpful in a few settings, but this assertion is patently false as atherosclerosis is well under way long before Calcium scores and angiography are able to identify it.
5. You don’t see lumen (Artery) narrowing until the damage is done. The main artery plaque is building in the endothelial space (behind the artery wall) long before a narrowing in the lumen occurs.
6. Plaque that has accumulated in the arteries starts well before the age of 10 years. If you don’t start preventative lifestyle treatment early, the problem will only keep getting worse, until either a cardio event occurs or the amount of plaque accumulates to a point that makes it so much harder to reverse.

Here are some facts about cholesterol and lipoproteins I hope you will find interesting:

Cholesterol is an organic sterol molecule in our body that is an essential structural component of all animal cell membranes. It is a crucial component in maintaining both membrane structural integrity and fluidity.

In addition, cholesterol also serves as a precursor for the biosynthesis of steroid hormones, bile acid and vitamin D. Cholesterol is the principal sterol synthesized by all animals. So we eat it, we make it, we store it, and we excrete it – all in different amounts.

The pool of cholesterol in our body is essential for life. No cholesterol = no life. Much of the cholesterol we eat is not absorbed and is excreted by our gut (i.e., leaves our body in a stool). Re-absorption of the cholesterol we synthesize in our body (i.e., endogenous produced cholesterol) is the dominant source of the cholesterol in our body. That is, most of the cholesterol in our body was made by our body.

Eating cholesterol has very little impact on the cholesterol levels in your body. It is carried around the body by a special protein-wrapped transport vessel called a lipoprotein. Lipids/fats are not soluble in blood so they are lipophobic. Lipoprotein are soluble in blood so they are said to be lipophilic and they can easily move within the blood stream.
As these lipoproteins vessels leave the liver they undergo a process of maturation where they shed much of their triglyceride “cargo” in the form of free fatty acids (and glycerol), and doing so makes them smaller and richer in cholesterol.

Special proteins, (apolipoproteins), play an important role in moving the lipoproteins around the body and facilitating their interactions with other cells. The most important of these are the apoB class, residing on VLDL, IDL, and LDL particles, and the apoA-I class, residing for the most part on the HDL particles. So they start as very low density lipoproteins, (VLDL) and after shedding triglycerides (TGs) and picking up cholesterol they end up as LDL.

Chylomicrons are the equivalent of VLDL, they take TGs and cholesterol from the gut out to adipose (Fat), cardiac and skeletal tissue. They also react with HDL to exchange cholesterol and TGs.

Cholesterol is transported in plasma in both directions, from the liver and small intestine out to periphery tissue and back to the liver and small intestine. (the gut)
The major function of the apoB-containing particles (VLDL, LDL) is to traffic energy (triglycerides) to muscles and phospholipids to all cells. After they do this their cholesterol is taken back to the liver to be either resynthesized or excreted through bile and stools. The apoA-I containing particles (HDL) traffic cholesterol to steroidogenic tissues, (to make hormones) adipocytes (fat tissue for storage) and ultimately back to the liver, gut, or steroidogenic tissue.

All lipoproteins are part of the human lipid transportation system and work harmoniously together to efficiently traffic lipids. This trafficking pattern is highly complex and the lipoproteins constantly exchange their core (Cholesterol and TGs) and surface lipids. (phospholipids)

Currently, most people in Australia, the United States (and the world for that matter) undergo a “standard” lipid panel blood test, which only directly measures Total Cholesterol, (TG), and HDL-C. LDL-C is measured or most often is estimated. ie TC – HDL-C = LDL- C

More advanced cholesterol measuring tests do exist to directly measure LDL-C (though none are standardized), along with the cholesterol content of other lipoproteins (e.g., VLDL, IDL) or lipoprotein sub particles.

The most frequently used and guideline-recommended test that can count the number of LDL particles is either apolipoprotein B (Apo B), (Note: you can get this test in Aust) or LDL-P using Nuclear Magnetic Resonance (NMR), which is part of the NMR LipoProfile. NMR can also measure the size of LDL and other lipoprotein particles, which is valuable for predicting insulin resistance in patients before changes are noted in glucose or insulin levels.

The progression from a completely normal artery to a “clogged” or atherosclerotic one follows a very clear path: an apoB containing particle gets past the endothelial layer into the subendothelial space. The particle and its cholesterol content is retained, immune cells called macrophages arrive to eat up the invader, an inflammatory response ensues “fixing” the apoB containing particles in place AND making more space for more of them. They then turn into foam cells. While inflammation plays a key role in this process, it’s the penetration of the endothelium and retention within the endothelium that drive the process.

The most common apoB containing lipoprotein in this process is certainly the LDL particle. However, Lp(a) and apoB containing lipoproteins play a role also, especially in the insulin resistant person. Note: Lp(a) is a LDL particle containing a protein, apoprotein (a). It is a nasty one because it gets into the sub endothelium quicker, stays there longer, is oxidized more easily and creates more of an immune response. Apo(a) retards the clearance of Lp(A) itself so is even more problematic. You can also test for this in Australia.
So if you want to stop atherosclerosis, you must lower the LDL particle number - Period.

After looking at all the available research it appears that smaller LDL particles are at greater risk for atherosclerosis than large LDL particles, all things equal. So just because your blood LDL cholesterol goes up it could be the larger less dangerous type of LDL (large and fluffy), but it is still the case that if you don’t know the number, you don’t know the risk.

LDL-C is only a good predictor of adverse cardiovascular events when it is concordant with LDL-P. In other words, when both are high. More often than not, LDL-C and LDL-P are discordant in patients that die due to a cardiovascular event, ie LDL-C low and LDL-P high. The lowest risk (and I hope doctors are reading this) is high LDL-C and low LDL-P.

Even though LDL size matters, if LDL-P goes up the relationship between size and cardiovascular events vanishes. The only thing that matters is the number of LDL particles – large, small, or mixed.

HDL-C and HDL-P are not measuring the same thing, just as LDL-C and LDL-P are not. Recent studies have shown that simple measurements of HDL cholesterol may not always reflect HDL function. So you can have normal HDL levels, but HDL function may be impaired. Therefore, measuring HDL cholesterol may not be the best method to assess HDL’s function in the body. Although incomplete, HDL cholesterol is still the most widely used measurement to assess HDL.

Secondary to the total HDL-P, all things equal it seems smaller HDL particles are more protective than large ones. As HDL-C levels rise, most often it is driven by a disproportionate rise in HDL size, not HDL-P.

In the trials which were designed to prove that a drug that raised HDL-C would provide a reduction in cardiovascular events, no benefit occurred: But, this says nothing of what happens when you raise HDL-P.

Don’t believe the hype: HDL is important, and more HDL particles are better than few. But, raising HDL-C with a drug isn’t going to fix the problem. Making this even more complex is that HDL functionality is likely as important, or even more important, than HDL-P, but no such tests exist to “measure” this.

Why is HDL considered good? HDL particles can take lipids (fats) out of the artery wall, and enlarges. It can then take that cholesterol/fat to other cells to be used or back to the liver to be re-used or excreted.

The complexity above, is probably the reason why every trial, that has tried to increase the concentration of cholesterol in HDL particles (i.e., raise HDL-C) has failed (big time) to reduce events. The value in HDL particles is almost assuredly in its functional capacity—ie what it is doing that might be cardio protective


What is it? Angioplasty opens blocked arteries and restores normal blood flow to your heart muscle. It is done by threading a catheter (thin tube) through a small puncture in a leg or arm artery to the heart. The blocked artery is opened by inflating a tiny balloon in it. The media explains it like a plumber clearing a blocked pipe, but unfortunately this is far from the truth. For those patients with a stable artery disease, local interventions can only relieve symptoms; they do not prevent future myocardial infarctions. 12 randomized trials in the US conducted between 1987 and 2007, involving more than 5,000 patients, have found no reduction in myocardial infarction attributable to angioplasty in any of its forms. And yet, despite this overwhelming evidence, the plumbing model, complete with blockages that can be fixed, continues to be used to explain stable coronary disease to patients, who understandably assume that angioplasty or stents will prevent heart attacks—which they patently do not. You still need to look at lifestyle changes to have any effect on death rates due to cardio vascular events.

Atherosclerosis takes a long time to evolve, and involves many steps. 50% of men and 33% of women in the USA has a cardiovascular event before the age of 64. Age is the biggest contributing factor because it is the accumulation of bad eating habits, smoking, too much alcohol, toxic chemicals and pollution over many years that does the damage. And it is all these things combined along with the constant exposure to LDL-P/ApoB particles that causes heart problems and deaths.

Unfortunately, most doctors will prescribe statins very readily, if LDL cholesterol levels are what they consider too high. I would suggest do your own research and consider all options before going down this path.

I hope this post explains and gives you a better understanding of the processes involved. The treatment is another matter. I have touched briefly in other posts about my nutritional views on treating heart disease and I will be posting more information about this in the coming months.

A last word from Dr Attia. If you sleep with a gun under your pillow in your house with your children, there is higher probability of an accidental shooting with a child (or anyone), but if that gun is loaded the risk goes up dramatically, Why? Not just because we have “more” information–we actually have very specific “new” information. We have information about the causative agent, the loaded gun. LDL-P and Lp(a)-P are the causative agents, and while other forces matter (e.g., inflammatory response), there is no getting around the fact that high LDL-P and Lp(a)-P are stacking the odds against you. The gun won’t pull the trigger on its own, but it’s still the causative agent. People are too quick to confuse “necessary and sufficient” with “necessary but not sufficient”– in both cases reducing the “necessary” component helps.

While I do not doubt that some people with high LDL-P and Lp(a)-P may be immune to the typical “rules” of atherosclerosis, we don’t have good enough tools to predict this, especially non-invasively.

So what do you do if your patient cannot change their lifestyle? The risk of doing something to lower these modifiable risks, even if that means taking drugs, must be weighed against the risk of doing nothing.

So it is amazing what a difference nutritional and lifestyle intervention can do, but it would be better to have your doctor with you going down this path instead of down the normal drug path. Hopefully this information will at least inspire individuals and doctors to take another look at the latest research about a topic that has become a major world wide epidemic.