Note to the reader: we just interviewed world renowned lipid expert Dr. Thomas Dayspring on the Gene Food Podcast. APOB was a hot topic on the show.
In New York City, yellow taxis shuttle people around the 5 boroughs.
Similarly, in our bodies, lipoproteins shuttle different types of fats around to various parts of the body.
Certain of these lipoproteins are composed of proteins known as apolipoprotein B, which is the protein that makes up the shell of particles like LDL and VLDL just as steel makes up the shell of the yellow taxis furiously driving all over the Big Apple.
And, as we’ll see, knowing your ApoB from your LDL-C from your LDL-P is absolutely essential if you want to gauge your risk of heart attack.
What are APOB and apolipoprotein B?
Before we really dig in, a word on nomenclature. Scientists abbreviate the protein apolipoprotein B as “ApoB.” The gene that provides the instructions for the body to make the protein is referred to as APOB.
APOB encodes for two forms of apolipoprotein B, namely apolipoprotein B-48 and apolipoprotein B-100.
These are shortened to ApoB-48 and ApoB-100 respectively.
ApoB-48 is a type of protein unique to chylomicrons, a little known lipid carrying particle, primarily found in the small intestine, whose job it is to help the body use fat right after a meal.
ApoB-100 is made in the liver and is the only type of apolipoprotein that affects low-density lipoprotein (LDL).
There is one ApoB protein for every LDL particle. ApoB helps to maintain the structural integrity of LDL particles, thereby enabling LDL to bind to receptors on the surface of cells.
The difference between ApoB and ApoA
When lipoproteins leave the liver, they typically contain both cholesterol and triglycerides. The lipoproteins then mature and jettison a whole lot of triglycerides as free fatty acids. This process means that the resulting lipoproteins are smaller and carry a higher concentration of cholesterol.
Apolipoproteins in the B class reside on LDL particles, intermediate-density lipoprotein (IDL) particles, and very-low-density lipoprotein (VLDL) particles.
Apolipoproteins in the A-I class are more normally found on high-density lipoprotein (HDL) particles.
ApoA-I-contianing particles transport cholesterol to fat cells and to steroidogenic tissues, i.e. tissues that can convert cholesterol into pregnenolone, such as the gonads and adrenal glands. ApoA-I-containing particles also transport cholesterol back to the liver and gut.
Why should you care about ApoB?
In general, a high level of ApoB, is associated with a higher risk of plaque and blood clot formation and corresponding coronary artery disease. Why? Because LDL particles transport cholesterol and triglycerides around your body.
Some LDL particles carry triglycerides and some carry cholesterol. The main role of ApoB-containing lipoprotein particles is to transport triglycerides around the body. This includes to muscles to be used as fuel. ApoB also helps transport phospholipids to all of our cells to maintain cell integrity and support cellular metabolism. In addition, ApoB plays a role in reverse cholesterol transport, collecting cholesterol from HDL and taking it back to the liver for processing.
So, LDL and ApoB are the good guys, right?
Not so fast.
When a lipoprotein particle containing ApoB gets beneath the cells that line the artery wall, otherwise known as the “subendothelial space,” an immune response is triggered. This begins the inflammatory process of atherosclerosis. The immune cells arriving in the artery cause an inflammatory response and the particles get stuck in the arterial wall. This also has the unfortunate effect of enlarging the space where more particles can get caught and stuck.
How to test your ApoB level
For some of us, our LDL-C levels map nicely with our ApoB levels. On a standard lipid panel, you’re likely to see results for:
- Total cholesterol (TC)
- Triglycerides (TG)
- High-density lipoprotein cholesterol (HDL-C)
- Low-density lipoprotein cholesterol (LDL-C)
Usually LDL-C will be measured or estimated.
So, you may be able to guestimate your ApoB level by way of your LDL-C level. However, high blood sugar and insulin resistance make a low LDL-C and high LDL particle level more likely. This would mean that ApoB and LDL-C don’t match. How can this be? Well, because you may have more LDL particles carrying triglycerides than LDL particles carrying cholesterol.
So, to more accurately gauge your ApoB level, you either need to run a lipid panel that tests specifically for ApoB or one that provides a total LDL particle count. If you’re in the U.S., check out Everlywell.com.
Remember, every LDL particle contains one ApoB protein. That said, your actual ApoB count may be a little higher depending on how much VLDL and IDL you have circulating, as these lipoproteins also contain ApoB.
What this all boils down to is that your LDL particle count represents the opportunities your body has to deposit fat in your arteries. The higher your ApoB (or LDL-particle) level, the more potentially dangerous lipids there are in your blood. In some cases, LDL-P levels may be ten times those of LDL-C.
Why does knowing your ApoB level matter?
Understanding that ApoB and LDL-C are not one and the same is hugely important. Why? Because the highest risk of coronary artery disease and major adverse cardiovascular events is seen in those with a high LDL particle count. LDL-C is only a risk factor for heart disease when it matches LDL-P and ApoB. 1 2
So, if you simply assume your ApoB level (and thus your LDL-P level) is the same as your LDL-C level, you’re living a potentially dangerous illusion.
If, however, you have blood work done that reveals a high ApoB level but a low LDL-C level, I’d be extremely concerned as this suggests a high overall LDL-P level, which puts you at increased risk for heart disease.3
What about ApoB mutations?
Mutations in the APOB gene can cause a variety of diseases. These include:
These diseases affect plasma cholesterol levels and ApoB levels.
In one study published in 2018, researchers found that APOB rs1042034 “T” allele and rs673548 “G” allele increased the risk of the Ischemic Stroke by about 27-29%. For those with the APOB rs693 “AA-AG” genotype, Ischemic Stroke risk was increased by around 52% compared to those with the more common “GG” genotype.4
In another study, researchers found a significant association between the C allele of rs693 and high familial cholesterol levels. Meanwhile, the dominant T allele appeared to confer a protective effect.5
In an earlier study, carriers of GG genotype of rs676210 had almost a two-fold (1.93 odds ratio) increased risk of myocardial infarct (MI) compared to carriers of AA genotype. In addition, those with the specific haplotype GTTGG (rs676210-rs2854725-rs11676704-rs3791980-rs2678379) had almost a three-fold increased risk (2.82 odds ratio) compared with ATTGA haplotype. 6
The researchers also found a significant association between APOB rs676210 and rs2678379 polymorphisms and plasma levels of ApoB in individuals who hadn’t had an MI. This suggests that even seemingly healthy adults with these APOB polymorphisms may have high ApoB levels and an increased risk of MI. 7
In another study, researchers found that Saudis with familial hypercholesterolemia were more likely to have the rs151009667 polymorphism. 8
In conclusion, ApoB is an important thing to measure alongside LDL-C and LDL-P. Focusing on LDL-C levels alone can give you a false sense of security about your risk of cardiovascular disease, heart attack, and stroke.
It’s also good to know if you have any SNPs affecting ApoB as these could dramatically increase your risk of cardiovascular problems and other health issues.
To find out more about why heart disease risk goes far beyond LDL-C, check out John’s post here