Why High ApoB Is A Ticket to Heart Disease, Part 1
High ApoB is the most consequential warning sign that you could suffer a heart attack. But what is it, and how can you test for it? I review the science and get Dr. Peter Attia’s take on why you must drive down ApoB.
High ApoB is the most reliable test to assess your risk for heart disease. It’s a better predictor for heart disease than high LDL-cholesterol, or low HDL-cholesterol, or even fractionalized LDL — and yet I bet you’ve never heard of it.
But you need to, because cardiovascular disease remains the leading cause of death worldwide, and an ApoB test can tell you if you’re vulnerable.
Let’s dig in…
ApoB stands for Apolipoprotein B. It is a “family” unit consisting of various forms of LDL. There’s a blood test that can tell you how much ApoB’s LDL-cholesterol components are in your bloodstream. It’s a test you need to take, because, as a 2021 study called, Apolipoprotein B and Cardiovascular Disease: Biomarker and Potential Therapeutic Target puts it:
“While LDL, the major cholesterol-carrying serum lipoprotein, is the primary therapeutic target for management and prevention of atherosclerotic cardiovascular disease, there is strong evidence that apoB is a more accurate indicator of cardiovascular risk than either total cholesterol or LDL cholesterol.”
Most of us under a doctor’s care know about blood tests for cholesterol measurements, such as the LDL (Low density lipoprotein) and HDL (high density lipoprotein). LDL-C is the cholesterol contained within LDL and HDL-C is the cholesterol contained in HDL.
It’s important to have both LDL and HDL in certain amounts, as they each serve an important purpose. Every cell in the body makes cholesterol; it’s an essential molecule for life. You’d be dead without it, because cholesterol makes up the cell membrane of every cell. It’s what enables cellular membranes to have fluidity and is the backbone for many of the hormones our endocrine system makes.
Cholesterol is produced by the liver and made by most cells, but it also needs to be able to move around in the body to build the structure of cell membranes. This happens by little ‘couriers’ called lipoproteins that transport it via the blood.
In order for this to happen, the body needs to solve a problem. You see, cholesterol is not water-soluble, so it doesn’t mix well with blood. Think about mixing oil and water; it doesn’t happen. In a similar fashion, cholesterol won’t move through the bloodstream like, for instance, glucose can. Glucose or ketones can travel through the bloodstream on their own, but triglycerides and cholesterol are only fat soluble and thereby can not.
The amazing body has a solution — it makes lipoproteins, spherical things that on the outside are water soluble and on the inside houses water insoluble (hydrophobic) substances; namely, cholesterol ester and triglycerides. These lipoproteins exist in two broad families identified by the protein signature that wraps around them:
- The ApoB-100 family, and
- The ApoB-48 family.
Generally, ApoB-100 is the family that’s important relative to heart disease. It consists of:
- LDL – low density lipoprotein transports cholesterol from the liver to cells. 80% of its total weight contains lipids.
- VLDL – very low density lipoprotein transport triglycerides from the liver to adipose tissue. 91% of its total weight contains lipids.
- IDL – intermediate density lipoprotein are not usually detectable in the blood. Its size is between VLDL and LDL. 91% of its total weight contains lipids.
- LP(a) – Lipoprotein little a, an LDL with another special lipoprotein wrapped around it called apolipoprotein(a).
Now, the reason I’m digging into the weeds here is because how much of what type of cholesterol is streaming through your arteries matters greatly. The parsed story line that HDL is good and LDL is bad is an incomplete narrative; you need the whole story in order to act appropriately to safeguard your health.
LDLs are not the only thing that causes atherosclerosis, and a high LDL score is not the most threatening. What makes you vulnerable for a cardiac incident is a high ApoB score. High ApoB can cause atherosclerosis, a disease whereby there’s a buildup of plaque within the cardiovascular system that can lead to a heart attack and death. This can happen via atherosclerosis, because it’s an inflammatory disease of the arteries that results in plaque formation, which can result in the rupture of this plaque, leading to an acute thrombosis or an acute occlusion.
OK, so the pertinent question at this point is, What’s the relative risks of each of the types of lipoproteins contained in ApoB?
Glad you asked.
Let’s begin with VLDL and LDL.
VLDL It’s created in your liver to carry triglycerides throughout the body so that cells can use it for energy. Eating more carbohydrates (sugars) than is used for energy can lead to excessive amounts of triglycerides in the body and high levels of VLDL in the blood.
Extra triglycerides are stored in fat cells and released at a later time when needed for energy. Some VLDL is cleared in the bloodstream. The rest is transformed into LDL by enzymes in the blood. LDL has fewer triglycerides and a higher percentage of cholesterol than VLDL does.
IDL doesn’t last long in your blood, so it’s usually not problematic. That leaves LP(a). LP(a) is the most damaging component of ApoB, and is why you need to test for ApoB. A high ApoB test result can mean you have a cardiovascular time bomb waiting to explode.
ApoB is a far superior measurement to LDL, and is the best biomarker available to predict cardiovascular risk, because it is the total concentration of all particles capable of inducing atherosclerosis.
Now, there’s an important point about ApoB that longevity expert and medical clinician Dr. Peter Attia expressed to podcaster Tim Ferriss that is worthy of your attention. After explaining what ApoB is, Dr. Attia addresses a concern about pushing cholesterol too low, given its aforementioned importance. He says that you can push ApoB quite low and still get beneficial effects, and that high ApoB is alarming.
What follows is an edited transcript of the ApoB part of a lengthy Dr. Attia/Ferriss interview. You can see the whole interview below.
“… there’s always a concern that if you lower ApoB, you’re lowering cholesterol, because if you have fewer of the particles that carry cholesterol, you have less cholesterol floating around the blood. But what most people don’t understand is that that’s sort of like saying, I’m going to reduce the number of cars traveling over this bridge… does that necessarily mean you’re reducing the number of cars in the city? Not necessarily, so most of the cholesterol in your body is not in the lipoproteins rummaging around through your veins; again, most of the cholesterol is still sitting inherently in the cells itself.
“If you took a person’s total cholesterol [which includes all forms of cholesterol, including that in ApoB and HDL] and it was 200 milligrams per deciliter, and you lowered it from 200 to 100, you would say god that’s a 50% reduction in your cholesterol. No, it’s a 50% reduction in your serum cholesterol [what’s in your blood], which might be like a 5 to 10% reduction in your total body cholesterol.
“The other thing to keep in mind is we are born with very very low levels of cholesterol. In a child, the ApoB concentration is probably in the ballpark of 20 to 30 milligrams per deciliter. By the time we’re adults, a level of 80 milligrams per deciliter would put you at the 20th percentile; meaning, 80% of people would have a higher number than 80.
“There’s no upside to having more ApoB, right, the upside is in having that number be lower and lower and lower. But until recently it wasn’t clear how low you could drive it [down]. There was a drug… that hit the market in 2014 or 2015; a class of drug called PCSK9 inhibitors and they work in a manner that’s distinct from all previous drugs that lower cholesterol. [The PCSK9 gene provides instructions for making a protein that helps regulate the amount of cholesterol in the bloodstream.]
“They work by inhibiting a protein that degrades LDL receptors on the liver. And by inhibiting this thing that degrades them, you get more of the LDL receptors on the liver. It pulls more of the LDL receptor, it pulls more of the ApoB-bearing particles out of circulation, mostly LDL particles, but also some LP(a) particles.
“With these trials we see people achieving levels of ApoB in the 10 to 30 range with no side effects, no consequences. Furthermore, these drugs were developed when populations of people were identified who naturally had mutations in PCSK9 that rendered their PCSK9 ineffective. So, this was basically a drug that was designed to mimic a genetic mutation found in people who over the course of their lives have no increased risk of any disease and simply have a decrease in their risk of cardiovascular disease. In fact, the risk of cardiovascular disease is virtually non-existent.
“… lower ApoB is synonymous with cardiovascular mortality, and even mortality associated with diabetes and … all-cause mortality. [This is] not surprising, given that cardiovascular mortality is the greatest cause of mortality in the developed world. If you take a big enough chunk out of that, you should improve all cause mortality, but nevertheless, … a number of very large cardiovascular trials… demonstrate this effect where lower is better; the lower the LDL goes where the ApoB goes, the lower the risk goes.”
Peter Attia’s bottom line on ApoB:
- It’s the most important test to take to determine your risk for arteriosclerosis, a significant marker for a potential heart attack.
- Importantly, an ApoB test measures your LP (a), the most damaging type of cholesterol.
- High ApoB is 80 mg/dL, but you should strive to get it much lower.
Click here to watch the Dr. Attia interview
The part about ApoB begins at time stamp 1:11.01.
I’ve been meaning to take this ApoB test since I learned about it about two years ago. For several years, I was able to convince my doctor to expand the typical LDL/HDL/Triglycerides test to include fractionalized LDL, as I discuss in my post, Why Your LDL Cholesterol Particle Size Determines Your Heart Disease Risk and What To Do About It. If I knew better then, knew the importance of ApoB, I would have asked him to give me that test.
I decided not to wait.
A week ago, I finally ordered the ApoB test from the Life Extension Foundation (LEF). The form arrived in the mail two days ago (pictured above), and now I must get to a Labcorp to get my blood drawn. Labcorp will send the results to LEF, and then they will email me a pdf file.
Click here to read about the ApoB test
The apolipoprotein B (ApoB) blood test measures apolipoprotein B100, the ApoB protein that is associated with three different forms of potentially dangerous cholesterol: low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL).
Research shows that ApoB may be a better predictor of heart disease than a standard lipid profile ordered by your doctor.
Apolipoprotein B (ApoB) is a protein involved in the metabolism of lipids and is the main protein constituent of all non-HDL cholesterol in your blood. These ApoB-containing lipoprotein particles are the most damaging to your arteries and include not only LDL cholesterol but, VLDL and IDL… ALL of which promote atherosclerosis.
Since each ApoB-containing lipoprotein particle contains one ApoB molecule, measuring ApoB levels gives a good approximation of the total number of atherogenic particles in your blood. The greater the number, the greater the risk of more cholesterol ending up in your artery wall and the greater the risk of artery calcification and heart attack.
Why measure only LDL? This test provides the critical particle count number you need for ALL of your bad ApoB.
Once I get my results back, I’ll write a follow-up (Part 2) to reveal my “score” and describe what can be done to lower ApoB, whether I have high ApoB or not.
If you’re not a Subscriber, become one (it’s free), so you can be alerted when Part 2 is published, as well as keeping up with ever-evolving science about how to live a long and strong life!
Last Updated on October 23, 2022 by Joe Garma