Table of Contents
What are lipoproteins?
Cholesterol is an essential substance in the body, used to make some hormones and cell membranes. It needs to be transported around the body in the blood, but it is a fat, so it is not soluble in water. The body gets round this by packaging cholesterol and other fats with proteins. These protein and fat packages are called lipoproteins. The proteins that form the backbone structure of these particles are called Apolipoproteins.
What is ApoB?
There are different types of Apolipoproteins present on different lipoprotein particles, for example high density lipoprotein (HDL) particles have an Apolipoprotein A1 (ApoA1) and LDL particles have an Apolipoprotein B (ApoB).
The ApoB molecule is found on a number of lipoproteins:
- Chylomicrons – fat carriers created by intestines after a meal
- Low density lipoprotein (LDL) – The main cholesterol carrying lipoprotein
- Intermediate density lipoprotein (IDL) – short lived lipoprotein made as VLDL loses triglycerides
- Lipoprotein (a) – an LDL particle with an Apo(a) protein attached to it.
- Very low density lipoprotein (VLDL) – Triglyceride rich particles produced by the liver. Often high in people with diabetes or insulin resistance.
There are 2 types of ApoB: ApoB 100 and ApoB 48. ApoB 48 is made in the intestine and is usually found on chylomicrons and ApoB 100 is made in the liver. ApoB100 us the most important when it comes to atherosclerosis. ApoB 48 is called this because it is 48% of the molecular mass of ApoB 100.
- Any particle that has an ApoB molecule attached to it has the potential to end up in the artery wall and cause atherosclerosis.
- ApoB is proportional to the number of atherogenic particles.
There is no need to do expensise nuclear magnetic resonance tests to assess your particle count. There is only 1 ApoB molecule per particle so the ApoB measurement is basically proportional with the number of atherogenic particles in your blood. The most abundant ApoB particle is LDL.
Therefore your plasma ApoB number represents all the particles in your blood that can cause atherosclerosis.
Is ApoB a better risk predictor than LDL-C?
ApoB is a more powerful predictor of the risk of heart disease and stroke than LDL-C1 . A Recent meta-analysis of over 233000 people showed that ApoB was the most powerful predictor of risk of cardiovascular disease, followed by Non HDL-C and then LDL-C.
Your ApoB number should be central to assessing your risk of heart disease and stroke.
What are the main causes of atherosclerosis?
There is never one single cause of atherosclerosis. The process of atherosclerosis involves damage to the arteries, ingress of ApoB particles into the artery wall followed by macrophages and an inflammatory process. Modifiable risk factors are risk factors that you can potentially change to manage your risk. Male sex is a risk factor but it is not modifiable.
The 3 main modifiable risk factors for atherosclerosis are:
- High blood pressure
- ApoB particles
The amount of atherosclerosis you develop is proportional to the concentration of ApoB particles in the blood and the duration of exposure of the artery walls to the ApoB particles.
How to measure ApoB
ApoB in the blood is a simple and cheap blood test. The result is given in either mg/dl or g/l. The mg/sl number is 100X that of the g/l. e.g. 1.06 g/l = 106 mg/dl
What is the difference between LDL-C cholesterol test and ApoB?
LDL – C measures the total amount of cholesterol in your LDL particles. This number is usually proportional to your LDL particle number. However, it doesn’t include other atherogenic particles like VLDL and IDL. In disease like diabetes or insulin resistance patients often have high VLDL levels and this is not captured by the LDL-C test. The ApoB test captures all the atherogenic particles in the blood in one test!
What is a normal ApoB level?
Normal ApoB levels vary with the age and sex of an individual. You can use my ApoB calculator here to find out how you compare with other people.
What is an optimal ApoB level?
For ApoB the lower the better. If you want to lower your risk the most you should be trying to get your ApoB below 60mg/dl.
When should I start lowering my ApoB?
Atherosclerosis is driven by the concentration of ApoB particles in the blood and the duration of exposure of the arteries to ApoB particles. We also know from autopsy studies in road traffic accident victims that atherosclerosis starts when you are young. Think in your teens or 20s! Therefore, if you want to lower your risk of cardiovascular disease, the earlier you start lowering your ApoB the better.
How can I lower ApoB?
ApoB can be lowered with certain lifestyle changes, but the most powerful method of lowering is with medication.
How can I lower ApoB with lifestyle?
The same measures that lower LDL-C, will also lower ApoB
How can I lower ApoB with medication?
Using medications is the most powerful way to lower your ApoB. Depending on how high your ApoB is to start with you may need a combination of therapies. Most of these medications increase the activity of LDL-receptors in the liver. LDL receptors pull ApoB particles out of the circulation.
- Statins – These drugs inhibit the enzyme HMG CoA reductase, this reduces the production of cholesterol in the liver. The liver then starts to pull ApoB lipoproteins (mainly LDL particles) out of the blood and also reduces the number of ApoB particles it produces.
- Ezetimibe – This blocks the reabsorption of cholesterol in the intestine which then increases LDL receptor mediated uptake of ApoB particles by the liver. This drug is particularly effective in patients that are hyper-absorbers of cholesterol.
- PCSK9 inhibitors – A very powerful antibody injection that increases uptake of ApoB particles by the liver. You need to take the injection once every 2-4 weeks.
- Inclisiran – A new drug that is injected once every 6 months! It is a small interfering RNA drug that increases the activity of the LDL-receptors in the liver and lowers ApoB.
If you want to lower your risk of heart disease and stroke, you need to know your ApoB and lower it. It is a cheap and simple test and should be the focus of your longevity strategies. Most people will need some form of medication to get it to very low levels.
- Sniderman, AD, Williams, K, Contois, JH, et al. (2011) A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes 4, 337–34