Apolipoprotein B (apoB) is the causative agent in atherosclerosis. If your apoB is low, you will not develop atherosclerosis. However, if your apoB is high, you could die young.

We know this because of genetic studies of people with different levels of apoB and their health outcomes.

What is Atherosclerosis of the heart?

Atherosclerosis is a progressive laying down of "plaque" in the wall of the coronary arteries.  Since the coronary arteries feed the heart, this can lead to three outcomes:

1. The plaque impinges on the artery. Thus, the plaque will decrease blood flow to the heart. This can lead to angina or a poorly working cardiac muscle.
2. The plaque can rupture (burst) into the artery. Next the body repairs this by clotting the blood. Thus,  the blood flows to that portion of the heart is stopped. Without blood flow, the heart muscle starves, and if the flow isn't restored, that part of the heart will die. This is a heart attack or myocardial infarction.
3. The plaque can have no result.  Meaning, it isn't stopping blood flow to lead to angina, and it doesn't occlude the artery.

What is in the plaque?

In the above artery, you can see the yellow cholesterol in the wall. This is a "soft" plaque, like porridge.

The plaque is not inside the vessel. The artery is lined by a layer called the intima. So how does cholesterol get from the inside of the blood vessel to behind the layer?

The Process of Atherosclerotic Plaque Formation

Lipoprotein Entry into the Arterial Wall: The process begins when ApoB-containing lipoproteins pass through the endothelial layer of arteries. Normally, this layer acts as a barrier, but factors like high blood pressure or inflammation can make it more permeable, allowing these particles to accumulate beneath the endothelial cells.

Retention and Modification: Once inside the arterial wall, ApoB lipoproteins are trapped by proteoglycans (components of the extracellular matrix). These retained lipoproteins undergo modifications, such as oxidation, which makes them more likely to trigger inflammatory responses.

Inflammatory Response: The modified lipoproteins activate endothelial cells and attract immune cells like monocytes. These monocytes enter the arterial wall and transform into macrophages. Macrophages engulf the modified lipoproteins, turning into foam cells, which are a hallmark of early atherosclerotic plaque.

Plaque Development: Over time, foam cells accumulate, leading to the formation of fatty streaks in the arterial wall. Smooth muscle cells migrate into the intimal layer of the artery, contributing to the formation of a fibrous cap that covers the plaque. This cap consists of connective tissue, calcium, and cholesterol deposits.

Progression and Complications: As the plaque grows, it narrows the artery and restricts blood flow. If the fibrous cap ruptures, it can lead to the formation of a blood clot (thrombus), which may block the artery entirely, causing a heart attack or stroke.

Preventing Plaque Formation

Understanding how ApoB-containing lipoproteins contribute to atherosclerosis underscores the importance of managing blood cholesterol levels. Lifestyle changes such as diet, exercise, and medications like statins can reduce LDL levels, lowering the risk of plaque formation and subsequent cardiovascular events.

Atherosclerosis is a gradual process that starts with the seemingly harmless entry of ApoB lipoproteins into arterial walls. By addressing the risk factors that promote lipoprotein retention and inflammation, the progression of atherosclerosis can be slowed or prevented.

LDL particle size

LDL particles can vary in size, and it was previously believed smaller, denser LDL particles were more atherogenic than larger, buoyant ones. However, research has shown that the number of LDL particles, regardless of size, is a more significant determinant of cardiovascular risk. Studies indicate that the concentration of LDL particles is more closely associated with atherosclerosis than the size of the particles themselves.

The ApoB Factor: Why It's a Big Deal

ApoB is a protein found on the surface of atherogenic lipoproteins, including LDL, VLDL, and IDL. Each of these particles contains one ApoB molecule, making ApoB a direct measure of the number of atherogenic particles in the blood. This measurement is crucial because it provides a clearer picture of the atherogenic burden in the bloodstream than LDL-C alone.

Why ApoB is the Star Player

Direct Measure of Risk: ApoB directly measures the number of atherogenic particles, providing a more accurate assessment of cardiovascular risk.

Independent of Particle Size: Unlike LDL size, which can vary and complicate risk assessment, ApoB consistently reflects the number of risk-contributing particles.

Predictive Power: Numerous studies have shown that ApoB is a better predictor of cardiovascular events than LDL-C or other traditional lipid measures.

ApoB: Direct Measurement of Atherogenic Particles

Apolipoprotein B (ApoB) is the main protein component of several lipoproteins, including low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and lipoprotein(a). Each atherogenic particle contains one molecule of ApoB, making ApoB a direct measure of the number of atherogenic particles circulating in the bloodstream.

Key Points:

Direct Indicator of Particle Number: Since each atherogenic lipoprotein particle has one ApoB molecule, measuring ApoB provides an accurate count of these particles. This is crucial because the more atherogenic particles present, the higher the risk of these particles penetrating the arterial walls and contributing to plaque formation.

Independent of Cholesterol Content:

The cholesterol content does not influence ApoB measurement within these particles. Therefore, it provides a clearer picture of cardiovascular risk, especially in cases where LDL cholesterol (LDL-C) levels might be normal, but the number of LDL particles (and thus ApoB) is high.

HDL-TG Ratio: A Marker of Lipid Metabolism

The HDL-TG ratio, which is the ratio of high-density lipoprotein cholesterol (HDL-C) to triglycerides (TG), is used as a marker to assess lipid metabolism and insulin resistance. A high HDL-TG ratio generally indicates a favorable lipid profile and a lower risk of cardiovascular disease. However, this ratio has limitations:

Indirect vs direct measure:

Indirect Measurement: The HDL-TG ratio provides an indirect measure of cardiovascular risk. It does not directly quantify the number of atherogenic particles but rather gives a sense of lipid metabolism status. While a low HDL-C and high TG level can indicate higher cardiovascular risk, it doesn't directly account for the number of atherogenic particles present.

Variability and Confounding Factors:

Several factors can influence the ratio, including lifestyle, diet, and metabolic disorders, which can confound its predictive value for cardiovascular risk. Additionally, HDL-C levels alone have not consistently been shown to correlate with reduced cardiovascular risk, as HDL particles can vary in functionality.

Why ApoB is More Important

Predictive Power: Numerous studies have shown that ApoB is a stronger predictor of cardiovascular events than the HDL-TG ratio. For instance, the INTERHEART study highlighted that ApoB levels were more predictive of myocardial infarction than other lipid markers, including the HDL-TG ratio.

Comprehensive Risk Assessment: ApoB accounts for all atherogenic particles, providing a more comprehensive assessment of cardiovascular risk compared to measures that only consider cholesterol content or ratios of different lipid components.

 Focusing on the Right Metric

In summary, the focus has shifted from LDL particle size to the number of atherogenic particles, as measured by ApoB. This shift is grounded in the understanding that cardiovascular disease risk is more closely linked to the number of these particles rather than their size or cholesterol content alone. Therefore, ApoB provides a more accurate and reliable measure for assessing cardiovascular risk.

Conclusion

While both ApoB and the HDL-TG ratio can provide valuable information about lipid metabolism and cardiovascular risk, ApoB is considered more important due to its direct measurement of atherogenic particles. This makes it a more reliable and comprehensive marker for assessing the risk of atherosclerosis and related cardiovascular events.

Citations:

Sniderman, A. D., & Tsimikas, S. (2014). Apolipoprotein B. Circulation, 129(11), 1112-1120.

Packard, C. J., & Shepherd, J. (1999). Lipoprotein heterogeneity and apolipoprotein B metabolism. Atherosclerosis, 141(1), 27-42.

McQueen, M. J., Hawken, S., Wang, X., Ounpuu, S., Sniderman, A., Probstfield, J., ... & Yusuf, S. (2008). Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study. The Lancet, 372(9634), 224-233.

Cromwell, W. C., & Otvos, J. D. (2004). Low-density lipoprotein particle number and risk for cardiovascular disease. Current Atherosclerosis Reports, 6(5), 381-387.

Mora, S., Otvos, J. D., Rifai, N., Rosenson, R. S., Buring, J. E., & Ridker, P. M. (2009). Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipids and apolipoproteins in predicting incident cardiovascular disease in women. Circulation, 119(17), 931-939.

Packard, C. J., & Shepherd, J. (1999). Lipoprotein heterogeneity and apolipoprotein B metabolism. Atherosclerosis, 141(1), 27-42.

Sniderman, A. D., & Furberg, C. D. (2008). Age as a modifiable risk factor for cardiovascular disease. The Lancet, 371(9623), 1547-1548.

Cromwell, W. C., & Otvos, J. D. (2004). Low-density lipoprotein particle number and risk for cardiovascular disease. Current Atherosclerosis Reports, 6(5), 381-387.

Sniderman, A. D., & Tsimikas, S. (2014). Apolipoprotein B. Circulation, 129(11), 1112-1120.

Harchaoui, K. E., Visser, M. E., Kastelein, J. J., Stroes, E. S., & Dallinga-Thie, G. M. (2009). Triglycerides and cardiovascular risk. Current Cardiology Reviews, 5(3), 216-222.

McQueen, M. J., Hawken, S., Wang, X., Ounpuu, S., Sniderman, A., Probstfield, J., ... & Yusuf, S. (2008). Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study. The Lancet, 372(9634), 224-233.

>> Dr. Terry Simpson: In the topic about heart disease, you're going to

hear a lot about cholesterol. And it

gets confusing, because you're going to hear about good cholesterol,

bad cholesterol, LDL, hidl,

apob, small size, large

size, what does it all mean?

You're going to hear people state that LDL isn't important, but

that the size of particle or the oxidation is important.

And while all of this gets obscure,

today we're going to make sense of the madness

and show you how size isn't

important.

I am, your chief medical explanationist, doctor Terry Simpson,

and this is fork U forked

university, where we make sense of the madness. Busting

a few myths and teach you a little bit about food

is not always medicine.

Maybe you heard about LDL being the bad

cholesterol and HDl being the good cholesterol. And we

have to check your HDl triglyceride level

on and on and on. It really gets

confusing. Stripping away the good and bad

labels, we know that cholesterol, first of all, doesn't just

float around in your blood. Cholesterol is oil based

or waxy. And since your blood is water

based, we have to carry the cholesterol in

something. And so the cholesterol is placed in these

little packages of protein, and

those proteins are classified by their weight in a

centrifuge. And over time, we found that these

low density lipoproteins, that those

packages are responsible for

leaving deposits in the walls of your

arteries. And those deposits are called

atherosclerosis. And if you get a bunch of them together,

it's called a plaque. And those

plaques, when they rupture, lead to a heart attack

or to a stroke, or if they impinge on the

artery, meaning they start decreasing the flow of the

artery to the heart, they lead to heart ischemia

or angina. So

LDL isn't a one size fits all villain.

All the LDL particles vary in size, density,

oxidation, et cetera. So we're going to sort

of strip away one of the more common myths that I

heard, that you have to worry about

LDL, particle size. As if you couldn't hear

enough. We're going to strip that away because you don't

need to care about the size anymore. Size of the

LDL particle isn't important. And you don't have to

remember these old terms, like pattern a, large fluffy

particles are good. Pattern B, small dense

particles, are bad. Because the recent

research has shifted focus from the LDL particle

size to one of the lipoproteins

that surrounds the cholesterol, called apolipoprotein B,

which we will call ApoB.

Think of it this way. If you want to

not have messy tea, you

put your loose tea in something

like a teabag. Think about the

teabag as being partially held

together by one of these apob molecules,

right? So every single teabag, or

LDL particle carries one of

these little proteins, that Apop protein. Think of the tea

as the cholesterol. But that protein is a

passport that allows that

teabag to enter into the cell

wall of the artery,

not just passively, but it's actively

transported in. If there's an LDL particle, it's actively

transported into this cell wall.

And if there are too many LDL, particles in

that cell to be metabolized by that

cell, it tosses the LDL particles

out the backside of the cell into the wall of the

artery between the first and second layer.

That's where they build up, that's where they oxidize,

and that's where they can ultimately get so large

that they impinge on the artery wall, leading

to less blood flow to, like, the heart

artery, or less blood flow to the brain,

which can cause ischemia, a heart attack, or stroke.

The key is how many apob

particles there are. Now, we used

to think that that was the answer. The size

of the particle. We used to think small particles.

Wow. They're the bad ones, because when we looked at the research,

we saw small particles had more atherosclerosis. Is this

confusing you? But think about this. The more small

particles you have, you're gonna have more

apob, because if you bake a lot of little tea

bags, you gotta sew it together with that apolipoprotein

b, and that's a problem.

The particle number gives us a count of

how many of these atherogenic particles there are.

We call them atherogenic because the ApOB

particle is the thing, the particle that

leads to atherosclerosis. Doesn't matter

how large, how much tea is in the

teabag, how much cholesterol

is in the LDL particle. What matters

is how many of them are circulating in your blood.

Now, I've, heard people say, well,

cholesterol's important. It is. Cholesterol's

used in every cell. It is. Cholesterol's used to

make steroid hormones, like testosterone, estrogen.

It is. Cholesterol's important to your brain. It

is. But too much cholesterol, like too much

water or too much salt, or too much blood

sugar, is bad. Too much

cholesterol leads to atherosclerosis.

Some people say God doesn't make mistakes. Well, I don't know if God

made a mistake or not. We're not going to live forever. But if

you want to live longer, you want to have less

atherosclerosis. There have been

a number of articles that have shown this, that it is

the number of apob particles,

nothing, not the size of

the molecule. And there's two ways of looking at this.

If you have a bunch of little tiny molecules of ldl, which

have small particles, and they get in and they're tossed out

to the back, well, it's going to take a lot of those

to build one large cholesterol particle which is

equally actively transported in. So

you have a lot of large, fluffy particles, you'll have a

faster buildup. Now, what are things that increase

apob in your body? One of them

is sugar. That's why

diabetics need to be under better control, because

more glucose in your blood, the more spikes you have, the more

insulin resistance you have, the more diabetes you have, you're making

more APOB particles. The more apob particles, the more

atherosclerosis, the higher your risk of heart disease.

That's all. That's as simple as that.

So here's the key. This month,

when you go to your doctor, APOB is the

test you want to ask for. They'll give you a standard

cholesterol panel. It'll have your hdl, your

ldl, your total cholesterol, your

triglycerides. Ask to get an

APOb test. And while you're at it, also ask to get a

PSA test, because this month, this month,

we want you to do cancer screening. So, American

Cancer Society, what's my number? Screen me,

etcetera. So there's been lots of

meta analysis of participants showing how APOB is a stronger

predictor of heart events than cart particle

size. And I won't bore you with it, but if you want to find out more of

the detail and more of those for the nerdy bunches of

you, and most of you are nerds, go to the blog associated with

this@yourdoctorsorders.com or four

q.com.

now, how can diet and lifestyle affect the

apob number? We already talked about refined grains,

but saturated fat like red

meat increases apob

particles. Lean meat,

plant based fats like olive oil and

avocado don't. They might actually

decrease APOb number. So changing your diet from

saturated fats to less saturated fats when you get

below 9%, we see that change.

I know the low carb people never like this because

they want to wave off cholesterol, because every

article out there shows that low carb and keto diets lead to

higher ldl numbers,

increasing the fiber in your diet. Soluble fiber, like

foods found in oats, beans, and fruits,

reduce the number of ldl and apob particles in your

bloodstream. How do they do that? Because here's

what happens when your liver

makes ldl. Because this cholesterol is made and you're packaged

in your liver, what happens is it doesn't

just throw it into your bloodstream. It makes

all these ldl particles and puts it into your bile.

Your bile is secreted by your liver and goes into your

intestine, and from your intestine, it goes into your

bloodstream. Now, when you eat more

fiber, the fiber binds

to those LDL particles, and those fibers

that bind to the LDL particles

passively go out of your backside

into the toilet. Right.

Diets that are high in processed carbs and sugar raise apob

levels. And so those diets also have less

fiber. So increasing the fiber in your diet not only makes

you feel full longer, it decreases your

apob particles. I'll give you another

example. Whole grains, brown

rice, quinoa,

oats, corn,

all have fiber that

decrease apob. Refined grains don't have

fiber. Lead to sugar spikes lead to more

manufacturing of apob. That's why refined

grains aren't good. That's why whole grains are.

Okay? Okay, so to wrap

this up, while we used to think the size of the

LDL particle was important, it really is apob.

Ask your doctor for an apob. That's how we

get a better picture of your heart. What should your levels be? In the

United States, we want your apob levels to be under 100.

In Europe, we want them under 70. We'll probably go to under

70. Why do we keep changing this every

year? Because we have discovered over time that the lower

your total cholesterol number is, the healthier

you are. Now, there are m those people who say, well, you know,

long live people have higher ldls.

Okay? If you get to be old, you can have a

higher ldl. But remember, there are many other things that

influence this. Meaning this. I'll

give you one example. There's a genetic

predisposition to people called the PCSK nine

transport system. And if you have a genetic

defect in that, you can have high ldl,

but you also have high ldl

receptors. Because you have high ldl receptors, you

don't have that much ldl in your body. It's cleared very

quickly. And those people live

long. Remember, longer lived people,

still die of heart disease, still die of cancer, still

have diabetes, still have cognitive decline. They

just put it off for a while.

So get your ldl down. Is there a

lower level? Well, we know below. I think it's 53. You're probably

not going to have heart disease. What do kids

need? What do you need to maintain the amount of

testosterone and keep your brain well? Remember your lDl.

Your brain makes its own cholesterol. It doesn't rely on your

liver. Your gonads

make your own testosterone and estrogen. They don't rely on your

liver. So don't listen to people who say, that's

all I terribly important because too much cholesterol, like

too much salt, like too much blood sugar is

deadly.

All right, go to my blog, yourdoctorsorders.com, or

fork u.com, to see all

of the references and you can look them up for yourself. This

episode was written and researched by me, doctor Terry Simpson.

And while I am a doctor, I'm not your doctor. Please

see your doctor, a western trained, non

chiropractic, non eastern trained

physician. And if you're curious about, what

your LDl APOB number is, please see your regular doctor for

that. Podcast is distributed by our friends

at Simpler Media than the pod God, Mister Evo

Terra. Our production is done by producer Girl Productions, who

insist on my hair being perfect even though we're not

doing video today.

Until next time, stay curious. And

remember, food can be a powerful influence on your

health.

This month is cancer screening month for

prostate cancer. See, we want you to know your PSA

number, just like I know my APOb number, which is 63.

My PSA number is three. We want it under four.

So I hope this month you go to the American

Cancer Society, get screened, find out your

psa number. Because after all, min 50

and over, we need to know the number. And I hope

yours is less than four. And be sure and check

out your apopee number. Also.

>> Speaker B: 2.97, I'm happy to report. And

yes, that is checked on a regular and frequent basis with

me. And thanks for the information on the

APOB. I'm never going to drink tea in a

teabag again.