If you are over 50, or ever had a health check or “health MOT” with your GP, you have probably had your cholesterol checked. The reason cholesterol levels are checked is because of its link to the narrowing of your arteries, a process called atherosclerosis. This process is what causes heart attacks and most strokes – which are the leading and third most common causes of death in the UK respectively. The fact that these remain the leading causes of death suggest that the medical profession has not quite mastered how to prevent this problem.

In this post, I will break down the reasons why the standard tests you have had done may not be very helpful in telling you your risk of atherosclerotic cardiovascular disease (ASCVD). As a result, standard medical practice can often fall short of effectively preventing ASCVD – heart attacks and strokes.

Before doing this, it is important for you to briefly understand what atherosclerosis is and how cholesterol is linked to it.

The biggest killer on the planet – atherosclerosis

Atherosclerosis is the disease by which our arteries thicken, harden, and ultimately become blocked. It is the leading cause of death and disability in the world. In fact it is a process that has been shown to begin in your teenage years! The disease starts as fatty plaques that build up in our vessel walls. Over many years, this build up leads to thickening of the wall and narrowing of the arteries. Eventually this can lead to a complete blockage of the artery, leading to events like heart attacks and strokes. The image below shows a diagram of this process occurring over many years.⁶

For the above to occur, 3 things are required:

1. Damage and dysfunction of the vessel wall to allow lipids in
2. Cholesterol to be deposited in the vessel wall
3. Inflammation in response to the above to spur on the whole process

What is cholesterol?

Cholesterol gets a bad reputation when it comes to atherosclerosis. Cholesterol itself is crucial for human life. It forms a major component of the membrane of every single cell in your body. It is also a basic building block for numerous critical hormones and compounds within the body. Cholesterol becomes problematic only when it ends up stuck somewhere it shouldn’t be, in the blood vessel wall.

Every cell in our body can make cholesterol for its own needs. In fact, only around 20-30% of the total cholesterol in our bodies is from a dietary source^1,2. The majority of cholesterol in our body is actually synthesised by our own body. Our bodies also need to be capable of transporting cholesterol and other lipids to tissues that may need more of it for various reasons at any given time. This creates a biochemical problem.

Lipids don’t dissolve in water. Therefore, cholesterol will not dissolve in the fluid that is our main method of transportation around the body – blood, which is mostly water. Think about putting olive oil into a glass of water – the olive oil is a lipid and so will not dissolve in the water, i.e. the two will not mix.

Transport Solutions

To solve this problem, our liver makes something called lipoproteins which are spherical capsules with an internal core of lipids and proteins on their surface. The surface proteins allow them to dissolve in blood, allowing them to be transported easily.

There are a number of different types of lipoproteins that serve different functions. The identity of a lipoprotein can be characterised by the proteins on its surface. These proteins are called apolipoproteins (a bit of a mouthful, I know) and they form a sort of signature of the identity of the lipoprotein.

The liver makes something called a very low density lipoprotein (VLDL) to carry various lipids around your body. This travels around your body in your blood and as it delivers its lipids to their destination, the VLDL itself evolves to form first an intermediate density lipoprotein (IDL) and ultimately a low density lipoprotein (LDL).

VLDLs, IDLs and LDLs all have exactly one copy of a protein called apoB on their surface, forming part of their unique apolipoprotein signature. VLDLs and IDLs do not live for very long before becoming LDLs, so at any given moment, most of the apoB containing lipoproteins circulating are LDLs. It is these apoB containing lipoproteins that are the bad actors when it comes to atherosclerosis. Helpfully as they all have one single apoB on their surface, if we count the number of apoB particles, we also then know the total number of problematic particles.

Now cholesterol is cholesterol, so statements about cholesterol being “good” or “bad” are strictly not true. What matters is where cholesterol ends up, and this is dependent on the lipoprotein carrying it. Thus if we had to simplify things for people, we should really be saying “good lipoproteins” and “bad lipoproteins”.

ApoB particles (most of which are LDLs) are the “bad lipoproteins”. There are other lipoprotein types but broadly speaking, the other main one that exists in our blood is the high density lipoprotein (HDL). The HDLs are generally considered the “good lipoproteins”, but their function is quite complex and our understanding of their role is significantly poorer than that of LDLs.

The standard cholesterol tests your doctor orders

When you get your standard cholesterol tests done, you will get something along the lines of the above image. Now let me talk you through what is actually measured.

What is measured is the amount of cholesterol contained in all the lipoproteins in total, and the amount of all cholesterol just in your HDL particles (HDL-C). The other most relevant result you will get is the amount of cholesterol in all your LDL particles – known as LDL-C. Importantly this value is usually NOT directly measured, but rather it is usually a calculated estimation based on various assumptions.

We will come back to why this is a problem later.

Shipping problems

Let’s think of LDL particles as ships, cholesterol as the cargo and the artery wall as the docks. If the ships are carrying and delivering their cargo effectively, the cargo should not be stuck in the docks – i.e. you don’t want cholesterol stuck in the artery walls.

Why then does the cargo end up stuck in the docks? Is it a problem of too much cargo on each ship or is it that there are too many ships in the port?

Interestingly, it turns out that the number of ships is far more strongly correlated with the degree of atherosclerosis than the total amount of cargo on all the ships. It’s almost as though too many ships cause a metaphorical traffic jam, resulting in the cargo becoming stuck in the docks – which in the case of cholesterol is very bad for you.

It’s a numbers game. Every time an apoB particle crashes against the vessel wall, it will either bounce back or it will penetrate the wall. The more apoB particles you have, the more chances you have of getting them into the wall and eventually depositing their cholesterol.

So we know that to most accurately try to predict your risk of ASCVD, we need to know the number of apoB particles. Why is it then that your standard cholesterol tests do not measure or even calculate this, but prefer to give you calculated LDL-C levels. There are many reasons for this, most of which don’t make much sense – cost and a lack of knowledge being just a couple.

ApoB or LDL-C – same difference?

Now one could argue that LDL-C and apoB number are likely to be closely correlated. In other words, if your LDL-C is high then apoB is also likely to be high, and vice versa. So there is no need to check both, right?.

This turns out not to be the case in a significant proportion of people, meaning that it is quite common to have an only mildly raised or even acceptable LDL-C (the standard blood test done) but a much higher apoB level, or vice versa. This is called discordance.

There are three main situations in which discordance is seen:

1. Metabolic syndrome – obesity, insulin resistance, high blood pressure – 1 in 4 adults over 50 in the UK have metabolic syndrome (Heart UK)
2. Insulin resistance or diabetes – Worldwide, the prevalence of insulin resistance ranges from 15.5 to 46.5%³. Insulin resistance is the precursor to diabetes.
3. People taking a statin – 7-8 million people take statins in the UK (British Heart Foundation, 2018) mostly by adults above the age of at least 40, of which there are around 30 million at last check in 2021.

The numbers above show that if you live in the UK (or any Western country for that matter), there is a good chance you fall into one of these categories. Therefore there is also a decent chance that your standard cholesterol markers may be missing the important data points in terms of trying to assess your risk of CVD. Worryingly, they may underestimate it significantly.

Anything else we need to know?

As well as the misleading information from standard cholesterol tests, there is also often an absence of other important lipid markers.

One such marker is Lp(a) (pronounced el-pee-little-a). This is a special type of LDL which is even more strongly atherogenic (causing atherosclerosis) than your standard LDL particle. Thus far there are no available treatments that can reduce the level of Lp(a) which is largely genetically determined. It is very helpful to know your Lp(a) status when we are deciding on how aggressively to manage and reduce an individual’s personalised risk of ASCVD, as it can represent a “hidden” risk.

Missing the boat – too short sighted

Half of all people hospitalised with a heart attack have LDL-C levels within the recommended target levels.⁴ How can this be? This may be because standard medical preventive measures and advice are relatively short sighted relative to the slow burn of atherosclerosis.

Standard medical prevention of ASCVD usually involves some sort of risk estimation of your risk of having a heart attack or a stroke in the next 10 years using variables such as blood pressure, cholesterol markers and smoking status. Generally if the risk is calculated at above 10%, the individual is advised to have medication to lower their cholesterol, like a statin. Below this level, you get advised to just “keep healthy”.

Such calculations are very heavily weighted with respect to age, i.e. age is the biggest variable that affects your risk. This means that most people in their 40s and even 50s will never cross the standard risk threshold of 10% no matter how bad their LDL numbers are.

Therefore people who haven’t had a heart attack or stroke will usually not be recommended to take a cholesterol lowering medication like a statin, until they are above around 60 years old and their risk rises above 10%. By this point, we have missed the chance to reduce their exposure to high LDL levels for several decades.

Atherosclerosis actually begins much earlier that people realise, in our teenage years, and takes 30-40 years or so of exposure to apoB particles to slowly develop into the killer that it can be. It therefore seems illogical to wait until somebody’s risk of a heart attack over the relatively short 10 year horizon is increased before trying to remove the causative problem. By that point, we have missed the boat!

We should be intervening much earlier in someone’s life based on the assessment of their 30, 40 or 50 year risk, or even lifetime risk. The problem is these are difficult to quantify. That is still no excuse to not at least check the most important metrics to assess someone’s risk – like apoB level (not LDL-C) and we should know everybody’s Lp(a) level, amongst other variables too.

Start steering your ship early – our long sighted approach

The reality is that when it comes to lipids and cholesterol, it is the cumulative exposure to apoB particles over a lifetime that ends up being the biggest driver of atherosclerosis. Interestingly (but not surprisingly) people who have genetic mutations that result in them having extremely low levels of apoB for their whole lifetime, never really get ASCVD. They also don’t seem to have any negative consequences of such a low apoB level.

Drugs that are available that lower apoB are not perfect and so we cannot fully eliminate your apoB particles and risk of ASCVD. However, starting early in the lifespan of an individual to decrease the lifetime exposure to high levels of apoB particles is perhaps the most powerful intervention we have to stand a chance. An analogy I give people is of the Titanic hitting the iceberg. Given enough time to steer the ship away from the iceberg, the catastrophe could have been avoided. If you start steering away too late however, you don’t have enough time to avoid a collision!

Here at Agami, we are able to get a detailed picture of your cardiovascular risk by checking your apoB, Lp(a) as well as markers of inflammation and metabolic health – all the fundamental factors that drive the process of atherosclerosis. This allows us to individualise and optimise your prevention strategy and offer proactive treatment to reduce the risk of you having a heart attack or a stroke in the long run.

Look out for an upcoming blog post on the the ways we suggest our patients optimise their lipid markers in the long run with diet, supplements, lifestyle and medications.

Contact us to arrange a free 15 minute consultation to discuss how we can help you optimise your long term health and thrive.

References:

1. https://www.health.harvard.edu/heart-health/how-its-made-cholesterol-production-in-your-body
2. Kapourchali FR, Surendiran G, Goulet A, Moghadasian MH. The Role of Dietary Cholesterol in Lipoprotein Metabolism and Related Metabolic Abnormalities: A Mini-review. Crit Rev Food Sci Nutr. 2016 Oct 25;56(14):2408-15. doi: 10.1080/10408398.2013.842887. PMID: 26055276. Link
3. Fahed M, Abou Jaoudeh MG, Merhi S, Mosleh JMB, Ghadieh R, Al Hayek S, El Hayek Fares JE. Evaluation of risk factors for insulin resistance: a cross sectional study among employees at a private university in Lebanon. BMC Endocr Disord. 2020 Jun 10;20(1):85. doi: 10.1186/s12902-020-00558-9. PMID: 32522257; PMCID: PMC7288486. Link
4. Varvel SA, Dayspring TD, Edmonds Y, Thiselton DL, Ghaedi L, Voros S, McConnell JP, Sasinowski M, Dall T, Warnick GR. Discordance between apolipoprotein B and low-density lipoprotein particle number is associated with insulin resistance in clinical practice. J Clin Lipidol. 2015 Mar-Apr;9(2):247-55. doi: 10.1016/j.jacl.2014.11.005. Epub 2014 Nov 28. PMID: 25911082. Link
5. Image from https://punecardiologist.com/atherosclerosis.php