Biomarkers 101 ApoB
Apolipoprotein B (ApoB) is the single best lipid test to assess for cardiovascular disease risk.
Apolipoprotein B, also known as ApoB, is single handedly one of the most important lipid tests that a doctor can run, especially when trying to assess Cardiovascular disease (CVD) risk. Unlike LDL-C, which is the cholesterol marker most doctors are used to testing, ApoB consistently outperforms LDL-C when it comes to identifying your risk from dying from heart disease due to hyperlipidemia (or high cholesterol). We are going to discuss a few important points here - enough to power you with the information to have an educated conversation with your doctor - but much will need to be reserved for a future blog post.
Why does ApoB matter and increase heart disease risk?
There are quite a few reasons why but essential it comes down to a few points.
For every LDL, VLDL and IDL particle there is one ApoB. In other words, every LDL, IDL and VLDL contain one ApoB on their surface. And since ~95% of ApoB are found on LDL particles, we ca assume that most of the ApoB we measure is approximately equal to the amount of LDL particles.
LDL particle are the lipids that travel around our blood stream and they are attached to ApoB. And because LDL particles are a fat, they can’t float around the blood freely (think of mixing oil and water). So ApoB acts as the protein to transport our cholesterol throughout the body - to our cells, organs, tissues and unfortunately to our arteries lining.
Without ApoB, these particles are unable to be transported around the body. And without ApoB they do not have the opportunity to contact the lining of our arteries (and other vessels) and contribute to atherosclerosis (hardening of the arteries).
Important Note: ApoB is necessary but not sufficient in the pathogenesis of atherosclerosis. Meaning, we need ApoB containing lipoproteins to cause atherosclerosis but it is not the only factor - inflammation, insulin resistance, genetics, the make-up of the LDL particles (if they are full of triglycerides (problematic) or lecithin (protective)), etc., are all equally as important.
When we take all of this into consideration, we learn that ApoB more than LDL-C is a much more important biomarker for assessing heart disease risk.
Isn’t LDL-C your bad cholesterol?
There is no such thing as good or bad cholesterol. Cholesterol is cholesterol - a necessary molecule for multiple functions in the body including hormone production (testosterone, estrogens, cortisol), bile production for digestion, vitamin D synthesis, and many more essential bodily functions. What makes cholesterol problematic is how it is trafficked and transported around the body. The cholesterol that exists in your LDL particles is no different than that that exists in your HDL particles or VLDL particles. What makes these particles different is the density (mass/volume), their lipoproteins that help transport them around the body and the amount or quantity of particles.
I heard that we need cholesterol and it doesn’t cause heart disease.
Our body absolutely needs cholesterol, but as we discussed cholesterol is a necessary molecule for multiple functions in the body. Cholesterol itself is not problematic or a cause of heart disease, but how that cholesterol is carried, transported and its destination in the body absolutely does impact CVD risk. This is why ApoB is important to measure because ApoB is a surrogate marker for LDL particles, which are the type of lipids that contribute to heart disease. There is ample amount of research conveying a strong correlation between ApoB and LDL particles and heart disease (in particular heart attacks and other major adverse cardiovascular events) [1, 2]. Whereas the evidence for LDL-C (what most doctors usually test) is not as strong.
Important note: When we refer to lipids, we are considering things like total cholesterol, LDL-C, HDL-C, triglycerides, lp(a), apoB and any other lipid-related marker. It is important to understand that cholesterol is a lipid, as is LDL-C. So when we mention cholesterol, we should be more specific and identify which lipid marker since cholesterol could be referring to multiple things.
So where does this idea of cholesterol does not cause heart disease come from?
This idea is likely derived from the mixed findings on LDL-C and heart disease risk [3], where one major study found that when monitoring 136,000 individuals who were hospitalized with coronary artery disease (CAD), about half of them had an LDL-C of less than 100 mg/dL [4]. I can see how this would be very confusing, and lead to questions as to whether “lowering cholesterol” is actually protective. I use the term, “lowering cholesterol,” because this is how many clinicians and the general public speak. But instead, I think it’s important to be selective with our choice of words because it impacts how these studies and discussions translate into clinical practice. I would instead suggest we say that I can understand how this would be confusing and lead to questions as to whether “lowering LDL-C” is actually protective.
A few points to consider:
The studies showing contradictory findings on LDL-C and CVD/CAD were looking at sick populations and individuals who likely already had some level of heart disease present.
Heart disease (CAD, CVD) is a multifaceted disease and not caused by just one factor. It is a combination of inflammation, dyslipidemia, blood sugar dysregulation (insulin resistance), lack of exercise, dietary factors, genetics, and the list goes on. All of which are practically impossible to account for in a study. But what we try to do is isolate certain factors in multiple different studies, put them together and then come up with an informed and evidenced-lead recommendation for clinicians.
The studies did not consider or measure ApoB.
Bringing us back full circle to ApoB - Looking at LDL-C vs. ApoB
This brings us back full circle to ApoB, and why it is much more informative and alone is a better indicator for heart disease risk. t is a very important biomarker and should not be ignored when it comes to assessing, preventing and treating heart disease. Standard measurements of lipid tests like LDL-C, total cholesterol, HDL-C, and triglycerides can be misleading when it comes to measuring the quantity of particles and heart disease risk.
For example, we have 2 people (A and B) and we measure their total cholesterol, LDL-C and ApoB. Person A and B can have the exact same LDL-C (e.g., 150 mg/dL) and total cholesterol (e.g., 250 mg/dL). Assuming all else is equal (age, gender, diabetes risk, etc.), some clinicians will assume that these two people have the same risk profile. But if Person A has an ApoB of 150 mg/dL and Person B has an ApoB of 75 mg/dL, then person B has a significantly lower risk of have a heart attack or other major adverse cardiovascular event (stroke, etc.).
But, if Person A and B had the same ApoB (90 mg/dL), but person A had a lower LDL-C, clinicians would assume that person A was at a lower risk but that is not necessarily true.
Why? Because ApoB is allowing us to indirectly measure LDL-particles which are highly concordant for CVD risk and especially more so than LDL-C.
References