Apolipoprotein B (apoB)

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

This process leads to formations of atherosclerotic lesions or plaques that may protrude into the lumen of the artery causing arterial narrowing, which may ultimately limit blood flow.

If this occurs in the coronary arteries, it may cause angina pectoris and if it occurs in the arteries of the legs, it may cause claudication.

Rupture of an atherosclerotic plaque may lead to thrombosis causing an acute occlusion of the artery. If this occurs in a coronary artery it may cause an acute myocardial infarction.

There are many factors that contribute to atherosclerosis, one of which is elevated level of cholesterol.

Although cholesterol is an essential compound, elevated plasma levels appear to play an important 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 levels of plasma cholesterol also appear to be an important contributor to atherosclerosis in humans, although the threshold level of plasma cholesterol that must be exceeded to produce clinically relevant disease appears to be much lower than that in animal models, possibly because lesion formation occurs over many decades.

Atherosclerotic clinical events, such as myocardial infarction are uncommon among individuals with lifelong very low plasma cholesterol levels.

It is important to emphasize, that it is lipoprotein that interact with the arterial wall and initiate the cascade of events that leads to atherosclerosis. Cholesterol is only one of many components of lipoproteins.  Therefore, measurements of total cholesterol are only indirect measurements of the lipoproteins that transport the bulk of cholesterol.

Measurements of the number of LDL-particles (LDL-P) appear more predictive of risk than the measurements of the cholesterol mass within these particles or LDL-cholesterol (LDL-C).

Although LDL’s seem to be the most atherogenic particles, it has to remembered that VLDL and other apoB – containing lipoproteins may also contribute to atherosclerosis.

Apolipoprotein B (apoB)

Lipoproteins are the particles that transport cholesterol and triglycerides in the blood stream.

Lipoproteins are comprised of proteins (apolipoproteins), phospholipids, triglycerides and cholesterol. The lipoproteins vary in the major lipoprotein present, and the relative contents of the different lipid components. ApoB is an important component of many of the most atherogenic lipoprotein particles.

ApoB occurs in 2 main forms, apoB 48 and apoB 100. ApoB 48 is synthesized mainly by the small intestine. ApoB 100 is the apolipoprotein found in lipoproteins synthesized by the liver. Therefore, from the viewpoint of atherosclerosis and cardiovascular risk, apoB100 is the important one. ApoB 48 is primarily found in chylomicrons.

ApoB 100 is found in chylomicrons, VLDL, IDL, LDL and LP(a) particles. All these particles are atherogenic. Each of these particles contains a single apoB molecule. Therefore, measurements of apoB represent the total burden of the main lipoprotein particles involved in the atherosclerotic process.

Usually, 85-90 percent of apoB represent LDL particles. Thus, apoB reflects particle concentration, similar to LDL-P.

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

Several studies have shown that apoB may be a better predictor of cardiovascular disease risk than LDL-C. Furthermore, it has been shown that apoB may be elevated despite normal or low concentrations of LDL-C. ApoB also appears to predict on-treatment risk, when LDL-C has been lowered by statin therapy. The INTERHEART study found that the apoB/apoA1 ratio is more effective at predicting heart attack risk, than either the apoB or apoA1 measure alone.

Apo B containing lipoproteins are the ones that are most likely to enter the wall of the arteries. They are capable of trafficking cholesterol into the artery wall, and if present in increased numbers they may be the main initiating factor in atherosclerosis. Retention of ApoB containing lipoprotein particles within the arterial wall is an essential part of the process.

The normal range for apoB is 40-125 mg/dL. Usually less than 100 mg/dL is considered desirable in low or intermediate risk individuals and less than 80 mg/dL is desirable in high risk individuals, such as those with cardiovascular disease or diabetes.

How to Lower ApoB

Many doctors will recommend the same general measures to lower apoB as they do for lowering LDL-C. Thus, reducing the amount of saturated fats and cholesterol is often recommended together with increased consumption of vegetables, fiber and mono-and polyunsaturated (omega-3) fatty acids.

Some studies have indicated that carbohydrate restriction may lower apoB, independent of whether the intake of saturated fat is low or high. LDL-C was not lowered by carbohydrate restriction in these studies, suggesting that diet may affect apoB and LDL-C differently.

Physical exercise has also been shown to lower apoB and positively affect the apoB/apoA1 ratio, but the effect on LDL-C appears to be much smaller.

ApoB levels can be reduced by cholesterol lowering drugs (statins).

Comments

  1. says

    Saturated fats have very little effect on cholesterol levels compared to other dietary factors. http://healthydietsandscience.blogspot.com/

    Interestingly, lower levels of LDL-C are associated with increased cancer risk. http://www.theheart.org/article/1375049.do If food elements (think omega-6 industrial seed oils) that lower LDL-C also increase cancer risk, lowering LDL-C in the wrong way might conceivably reduce the heart attack death rate by increasing cancer deaths. Another important consideration is evidence that higher LDL-C levels are associated with preservation of lean muscle mass. Hence, trying to lower LDL-C by exercising may be an exercise in futility. http://www.eurekalert.org/pub_releases/2011-05/tau-cn050511.php

    Then there’s this: http://perfecthealthdiet.com/wp/wp-content/uploads/2011/06/O-Primitivo-Cholesterol.jpg

    • Doc´s opinion says

      Thanks David for these useful comments. By focusing so much on cholesterol in itself being harmful, we have become quite confused through the decades. This has sometimes lead to misunderstanding and unnecessary debates. Although the epidemiological studies indicate an association between cholesterol and cardiovascular risk, the data is confusing, not least when it comes to total mortality, where we have seen that those with the lowest cholesterol levels have high mortality. This is very well demonstrated in your last reference. Furthermore, the possible association between low cholesterol and cancer has never been really shut down as you also point out.

      There is really no reason to see cholesterol as a harmful substance. It is only when cholesterol, bound to atherogenic lipoproteins becomes trapped within the arterial wall, that it becomes a part of the pathophysiological process of atherosclerosis. Atherosclerosis does not occur in the absence of cholesterol. LDL is the most atherogenic particle and this lipoprotein contains cholesterol. That does not mean that cholesterol is bad. Similarily, atherosclerosis would not occur without the response of our immune system. Of course this does not mean that our immune system is bad. On the contrary, it is essential for life. Cholesterol that is bound to nonatherogenic particles, such as HDL is not associated with high cardiovascular risk, further supporting the fact that cholesterol in itself is not the problem

      Lipoproteins play an essential role for the initiaton and progression of atherosclerosis. Therefore it is very important for us to understand what regulates the production and clearance of atherogenic lipoprotein particles and how these mechanisims may be influenced. LDL-C is only a measure of the cholesterol mass within LDL-particles. Thus, LDL-C only indirectly reflects the atherogenic potential of LDL particles. ApoB and LDL-P on the other hand reflect the number of atherogenic particles, with no mention of cholesterol mass. Therefore apoB and LDL-P are better risk predictors than LDL-C.

    • Doc´s opinion says

      Hi Zepp, Yes, I do follow Peter Attia´s blog.
      “Läser också LCHF magazinet varje gång jag besöker Sverige vilket är rätt ofta.”

  2. Edith Nir says

    I was wondering if you address the role of Lp(a) and how to address having a very high value (mine is 425!). Thanks.

  3. Susan says

    After a car accident in 2008 I began having daily headaches and then migraines. Not one to want to be on medications, I decided to try the ketogenic diet hoping that would help.

    I have been following a ketogenic diet for the past year (more strictly at some point that others- but recently very good) and I have since taken myself off of my daily migraine medications!

    I have had my second blood test over the last year and although my general cholesterol numbers are good, my lipid panel for Apo B and LDL-P have gotten worse.

    My basics – 48 yo, good general health, pilates 3x wk, about 15 lbs overweight- but have lost 25 so far

    Numbers from 1st test to 2nd blood test.

    LDL-C from 131to 123
    HDL-C from 86 to 93

    with and overall of 215

    Triglicerides from 64 to 52

    but what is critical is -

    Apo B from 92 to 94 from bad to worse

    LDL-P 1395 to 1511 again bad to worse.

    The most specific information I have found has been on your site- thank you! But I am concerned as it was said that the ApoB and the LDL-P are more critical biomarkers for CVD.

    Should I be worried?? I want to continue with this lifestyle, but need to make sure I am staying healthy and safe in my diet choices and have not been able to find any local doctors ( I live in Los Angeles, CA ) who specialize in the ketogenic diet who aren’t specific to treating Epilepsy.

    Your insight is greatly appreciated!

    Susan

Let me know what you think!