Apolipoprotein B (ApoB) and Risk of Heart Disease

Estimated reading time: 7 minutes

Apolipoprotein B (ApoB) is a protein that plays an important role in the development of heart disease. Elevated blood levels of ApoB indicate an increased risk.

Actually, ApoB may be a stronger predictor of risk than commonly used lipid markers such as LDL-cholesterol (1).

Apolipoprotein B (ApoB) and Risk of Heart Disease

ApoB is an important component of lipoproteins that participate in the formation of atherosclerosis.

To help you understand the role of ApoB, I will start by briefly explaining the role of lipoproteins in atherosclerosis. I will then discuss the apolipoproteins and their different classes. Finally, I will explain the role of ApoB and how it can be used to assess the risk of heart disease.

Atherosclerosis

Atherosclerosis may be described as chronic inflammation of the arterial wall. It is caused by a complex interplay between lipoproteins, white blood cells (macrophages), the immune system, and the arterial wall’s normal elements.

Atherosclerosis is initiated when an apoB-containing lipoprotein particle is caught in the vessel wall. This leads to an inflammatory cascade, resulting in the progression of atherosclerosis.

Atherosclerosis leads to the formation of plaques within the walls of the arteries. These plaques may subsequently cause blockages and limit blood flow to tissues and organs such as the heart and the brain.

An atherosclerotic plaque rupture may lead to thrombosis (blood clotting), causing an artery’s abrupt occlusion (blockage). If this occurs in a coronary artery, it may cause an acute myocardial infarction (acute heart attack).

Cholesterol and Lipoproteins

Although cholesterol is an essential substance for most cells in our body, elevated blood levels may play a role in the initiation and progression of atherosclerosis.

In animal models, atherosclerosis will not occur in the absence of greatly elevated levels of plasma cholesterol. High blood levels of cholesterol also appear to be an important contributor to atherosclerosis in humans.

However, the role of cholesterol is most often oversimplified. Many individuals with high blood cholesterol never develop heart disease, and many patients with heart disease don’t have high cholesterol levels.

In fact, cholesterol’s role in heart disease appears to be determined by the lipoproteins that carry the cholesterol in the  bloodstream rather than the cholesterol itself.

Let me explain.

Because fats are insoluble in water, cholesterol can not be transported in blood on its own.

The body’s solution to this problem is to bind fats to proteins that function as transport vehicles carrying different types of fats such as cholesterol, triglycerides, and phospholipids. These combinations of fats and protein are termed lipoproteins

It is important to emphasize that it is the lipoproteins (not the cholesterol) that interact with the arterial wall and initiate the cascade of events that leads to atherosclerosis (2).

Cholesterol is only one of many components of lipoproteins.  Therefore, measurements of total cholesterol provide little information about the amount and types lipoproteins particles in the circulation.

There are five major types of lipoproteins; chylomicrons, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)

Lately, the role of another lipoprotein, called lipoprotein(a) or Lp(a), has been highlighted (3).

A standard lipid profile will tell us how much cholesterol is being carried by the different lipoproteins. Hence, the level of LDL-cholesterol and HDL-cholesterol will tell us how much cholesterol is found within LDL and HDL particles, respectively.

Scientific data tells us that there is a strong correlation between LDL-cholesterol and heart disease risk, although this has been debated by some investigators (3, 4).

However, measurements of the number of LDL-particles appear more predictive of risk than the cholesterol mass within these particles (represented by LDL-cholesterol) (5,6). 

Apolipoproteins

Lipoproteins are comprised of proteins, phospholipids, triglycerides, and cholesterol. However, the lipoproteins vary in the major lipoprotein present and the different lipid components present.

Different lipoproteins contain different apolipoproteins. The type of apolipoprotein present determines the structure and function of the lipoprotein.

There are several classes of lipoproteins and many subclasses (7).

I’ll just mention a few examples.

ApoA1 is the major protein component of HDL (8).

ApoA5 is a marker of increased triglyceride concentrations and a risk factor for heart disease in some populations (9).

ApoD has antioxidant and anti-inflammatory activity. It may play a role in diseases of the nervous system and the aging process (10).

ApoE has several subclasses. Human ApoE exists as three common isoforms, ApoE2, ApoE3, and ApoE4 (11).

ApoE4 is a major genetic risk factor for late-onset Alzheimer’s disease (12).

Lipoprotein particle
The type of apolipoprotein present determines the structure and function of the lipoprotein. ApoB100 is an important component of lipoproteins that promote atherosclerosis.

Apolipoprotein B 

Retention of ApoB containing lipoprotein particles within the arterial wall is an essential part of the early atherosclerotic process.

Lipoproteins that promote atherosclerosis are termed atherogenic. ApoB is an important component of all atherogenic lipoproteins.

Human ApoB has two main forms, apoB48 and apoB100. ApoB48 is synthesized mainly by the small intestine, and ApoB 100 ,is synthesized by the liver (13).

From the viewpoint of atherosclerosis and cardiovascular risk, apoB100 is the important one.

ApoB 48 is primarily found in chylomicrons whereas ApoB 100 is found in chylomicrons, LDL, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and Lp(a) particles.

Atherogenic lipoproteins such as LDL, VLDL, and Lp(a) all contain one ApoB molecule per particle. Hence, measurements of ApoB reflect the number of atherogenic particles.

On the other hand, HDL does not contain ApoB and is not atherogenic. In fact, HDL appears to play a protective role, and high numbers of HDL particles are associated with less risk of heart disease (2).

As mentioned before, ApoA-1 is the principal apolipoprotein on the HDL paritcle.

Thus, the ApoB/ApoA-1 ratio represents a measure of the balance between particles that promote and protect from athersclerosis.

The ApoB/ApoA1 ratio may be more effective at predicting heart attack risk than either the apoB or apoA1 measure alone (14).

Usually, 85-90 percent of apoB is found in LDL particles. Thus, apoB reflects LDL particle number, similar to LDL-P.

Evidence suggests that apoB is a better tool to predict cardiovascular risk than LDL-cholesterol and non-HDL-cholesterol (15).

Furthermore, apoB may be elevated despite normal or low levels of LDL-cholesterol (16).

ApoB also appears to predict risk when LDL-cholesterol has been lowered by statin therapy.

Normal Range For Apolipoprotein B

Although measurements of apoB are not widely available, the assay has been standardized and does not require a fasting sample.

The normal range for apoB is 40-125 mg/dL.

ApoB levels are higher in men than women and tend to increase with age.

Here is how apoB levels are looked at in terms of risk of heart disease:

  • Less than 130 mg/dL (1.3 g/L)is considered desirable in individuals without risk factors.
  • Less than 110 mg/dL (1.1 g/L) is considered desirable in low or intermediate-risk individuals.
  • Less than 90 mg/dL (0.9 g/L) is desirable in high-risk individuals, such as those with heart disease or diabetes.

How to Lower Apolipoprotein B

Many experts will recommend the same general measures to lower apoB as they do for lowering LDL-cholesterol. Hence, eating less saturated fat and cholesterol from meat and dairy products is often regarded as a first step. Furthermore, increased consumption of vegetables, fiber, and mono-and polyunsaturated (omega-3) fatty acids is recommended.

However, some dietary interventions may affect LDL-cholesterol and apoB differently. For example, some studies have indicated that carbohydrate restriction may lower apoB, independent of whether the intake of saturated fat is high or low (17).

Patients with high levels of triglycerides and low HDL-cholesterol may have high apoB levels despite normal or low LDL-cholesterol.  These patients may derive most benefit from low-carbohydrate diets (18).

Cholesterol lowering drugs such as statins, ezetimibe, and PCSK-9 inhibtors usually lower apoB levels.

Physical exercise has also been shown to lower apoB and positively affect the apoB/apoA1 ratio (19).




8 thoughts on “Apolipoprotein B (ApoB) and Risk of Heart Disease”

  1. quote:
    Atherosclerosis is initiated when an apoB-containing lipoprotein particle is caught in the vessel wall.”

    The immediate questions must be: why (is it caught)? what (under what conditions)? how (it is caught (mechanism))?

    why is nothing else apparently caught?

    Thanks

    Reply
    • That’s the million dollar question. We have to assume that many factors are involved; the status/permeability of the endothelium, the number of apoB containg particles, external facors like smoking, the presence of diabetes etc.

      Reply
      • Sorry, I am slow to respond.

        Is the initiating “event” an injury to the endothelium (ultimate cause).
        Therefore, we need to understand that aspect first – there are potentially many causes (of injury) events.
        To start with, perhaps a weakened endothelium due to “shortened” glycocalyx caused by a hi-carb diet?
        Or perhaps low vitamin C levels.
        Or as you imply many different things like smoking.

        So the key question is:
        Can the apoB-containing lipoprotein particle cause the injury or does this particle arrive on the scene subsequently (deliberately as part of the repair process or accidently?) ?
        .

  2. Great Content!
    Since I am pretty much new to blog writing this was really helpful in understanding more about heart diseases and I’m really excited to dig deep more and curate valuable context.
    Keep up the good work.

    Reply
  3. Tough when this test is rarely available. Low carb diets can increase LDL-C through legitimate processes – but LDL-P remains uncertain.

    More sand, but how many trucks?

    Reply

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