High cholesterol is the most important causal factor for atherosclerosis. Full stop. As such, we have historically placed a bright spotlight on LDL cholesterol as the bad, artery-clogging cholesterol. This is typically what has been measured clinically, serving as our primary target, as well as focused on in research trials. Recent studies, however, have moved beyond LDL cholesterol to examine more precise measures of atherosclerotic risk due to cholesterol. Literature has suggested there may be another more accurate marker for risk due to atherogenic lipoproteins and that is apolipoprotein B (aka apoB). Let’s explore why this is, the differences between LDL cholesterol and apoB, and end with a discussion on when and why you should have your apoB level checked.

What is apolipoprotein B (apoB)?

Before we talk about apoB, let’s first briefly touch on lipoproteins. Lipoproteins transport cholesterol and triglycerides from the liver to the tissues for utilization. Think of them as cholesterol transport vehicles. There are six different types of lipoproteins – chylomicrons, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), lipoprotein(a) and high-density lipoprotein (HDL). 

The main atherogenic lipoproteins are VLDL, IDL, LDL, and Lp(a). 

While they differ in the amount of cholesterol or triglycerides they carry, a constant between the lipoproteins is that they require proteins (apolipoproteins to be exact) for stability, transport, and metabolism. Exactly one apoB100 particle is found in each atherogenic lipoprotein. 

In most circumstances, approximately ¼ of atherogenic lipoproteins are VLDL and ¾ of atherogenic lipoproteins are LDL, however, in certain circumstances (notably with insulin resistance and hypertriglyceridemia), the contribution of VLDL can become more significant. Of note, there is an apoB48 as well,which is found on chylomicrons - however, transit time is so low that they are not a meaningful contribution to apolipoprotein b levels nor atherosclerosis development.

ApoB and atherosclerosis

The fundamental first step in the development of atherosclerosis is the trapping of cholesterol and triglyceride-containing apoB particles within the arterial wall. You can read more about the process of atherosclerosis in a prior blog post here, but the TLDR version is this - 

The higher the concentration of apoB particles in the arterial lumen, the more will diffuse into the arterial wall. Once in the arterial wall, many get trapped and the cholesterol within them deposits into the wall. This is the early stages of plaque build up. The amount of build-up within the arterial wall is determined by the number of apoB particles that are trapped. Additionally, an atherosclerotic plaque will grow - leading to plaque progression - with continued exposure to apoB lipoproteins.

What is the difference between the conventional lipid panel and measuring apoB?

As there is exactly one apoB on each of the atherogenic lipoproteins, measuring apoB determines the number of atherogenic lipoprotein particles. 

So what does the standard lipid panel measure? A standard lipid panel includes measurements of total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides.  The LDL cholesterol is actually an estimation of the amount of cholesterol contained within LDL particles. Read that again as it’s key to understanding this.

This can be problematic for several reasons

1.  LDL cholesterol is estimated with an equation. Particularly in those with diabetes or high triglycerides (> 177 mg/dl), this equation can be inaccurate and underestimate the actual LDL level, which in turn, would underestimate atherosclerosis risk. 

2. Particle cholesterol content is variable among different atherogenic lipoproteins. Risk calculators assume a constant concentration. We’ll talk more about this below. 

ApoB is a direct measure of the atherogenic lipoprotein number rather than an estimated measurement of the amount of cholesterol contained within the particles.

Studies have suggested apoB is a better marker for atherogenic risk in a variety of ways. It has been demonstrated to be an independent risk factor for heart attack. Additionally, it has also been shown that reducing apoB levels by statin or non-statin therapy reduces poor cardiovascular outcomes. It also performs better than LDL cholesterol when assessing cardiovascular risk. All of this is not to say that LDL reduction isn’t beneficial, it is. But it appears that the magnitude of that benefit is dictated by the corresponding reduction in apoB. 

LDL-cholesterol and apolipoprotein B discordance

If the amount of cholesterol per apoB-containing lipoprotein particle is consistent throughout the body, LDL and apoB are concordant. However, in a substantial number of people, the mass of cholesterol within the apoB particles can vary substantially. This is because the apoB particles can either be enriched in cholesterol or depleted in cholesterol -  in this situation, the values will be discordant.

I typically explain the situation to patients as this. Picture two people with the same LDL cholesterol of x mg/dL. This amount of cholesterol can be packaged in 5 large LDL particles or 10 small LDL particles. The person with 5 large particles is concordant, and their LDL cholesterol reflects their true risk due to atherogenic particles. The person with the 10 small particles is discordant, and their LDL cholesterol does not accurately reflect this risk. 

When LDL cholesterol is either low or normal, but apoB is high, this is a high risk discordance - the person with 10 small particles in the example above.  It is in this situation in which measuring apoB is particularly important, as the elevated apoB (and not their LDL cholesterol) reflects an individual's true atherosclerosis risk. If they just measure their lipid panel, their LDL cholesterol will reflect low or normal risk - entirely missing that they have unchecked atherogenic lipoproteins. This occurs most often in those with insulin resistance, diabetes, obesity, and elevated triglycerides.

Should you check your apoB?

The European Society of Cardiology and European Atherosclerosis Society in 2019 recommended apoB to be the preferred measurement to refine residual risk in those with normal LDL. It also gave a strong recommendation for measuring apoB in those with high triglycerides, diabetes mellitus, obesity, metabolic syndrome, or very low LDL levels. They went further to suggest targeting LDL < 100 mg/dl and apoB < 75 mg/dl in individuals at high risk for atherosclerosis, and LDL < 70 mg/dl and apoB < 60 mg/dl in those with very high risk.

While the 2018 American Heart Association/American College of Cardiology guidelines do not encourage routine testing, they do state that an apoB > 130 mg/dl should be considered a risk-enhancing factor.

In my practice, I use it routinely. It is quite cheap (not covered by my insurance, I was charged $25 recently), easy to add on to the routine lipid panel, and is often very informative for aggressive lipid control. If you’ve never had it checked, you should consider asking your doctor about adding it on next time they check your lipids - this is particularly important if you fall into one of the higher risk categories for discordance.