Lp(a) Awareness Day 2024.

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Cardiovascular disease (CVD) is the leading cause of death and a major contributor to disability across the world. The total number of deaths related to CVD in 2019 was more than 18.5 million1. In the 1940s and 50s it was shown that high levels of LDL Cholesterol (LDL-C), or bad cholesterol, increased the risk of heart disease. In the decades since we have taken massive strides in our understanding and ability to treat CVDs, but there is still a lot we don’t know. One such advance has been the discovery of lipoprotein(a), otherwise known as Lp(a), in 1963. In the last 10 years, our understanding of this ambiguous lipoprotein has flourished. It’s now clear that Lp(a) has a causal relationship with CVD2.

Those with the highest levels of Lp(a) are at a 1.5x increased risk of cardiovascular-related death, 1.6x risk of stroke, and up to 4x risk of heart attack when compared with those with the lowest levels3. Lp(a) levels are determined by genetics meaning there isn’t much you can do to reduce this risk. However, by lowering your other CVD risk factors, you can take steps to reduce your overall risk.

Atherosclerosis is a condition where arteries become clogged and hardened due to plaque buildup, significantly increasing the risk of CVDs like heart attacks and strokes3. It starts with damage to the artery’s inner lining, often caused by high levels of LDL-C, leading to inflammation and the accumulation of fatty deposits. Over time, these deposits grow into plaques, which can narrow arteries, reducing blood flow. Plaques may also rupture, forming clots that can further block blood flow3. A useful analogy here is to think of bad cholesterol as an army besieging a city. The larger the army, the higher the risk of the city’s defeat. Similarly, the higher your LDL-C levels, the higher your risk of suffering a CVD-related event. Lp(a) is also a major contributor to CVD risk2., however, many people haven’t even heard of this molecule.

The Emperor and The General.

We can take the metaphor of a besieged city even further. Most of us have heard of Genghis Khan, the founder and first Great Khan of the Mongol Empire. He is known for is his military conquests and the establishment of an Empire that would become the largest contiguous Empire in history.

We can use Khan to represent LDL-C, the bad cholesterol widely known to the public and medical professionals for its role in developing CVD. Just as Genghis Khan’s actions and leadership were directly visible and had a widespread impact, LDL-C’s contribution to plaque buildup and heart disease is well-documented and the primary target of many therapeutic interventions.

A character from history you are less likely to have heard of is Subutai the Valiant. Subutai was the primary strategist and general of Khans’ armies. After his humble upbringing as the son of a blacksmith, Subutai quickly climbed the ranks. He later led over 20 campaigns, seeing him conquer more territory than any other commander in history.

Subutai represents Lp(a) in this analogy. Lp(a) is a potent and independent risk factor for cardiovascular disease that operates behind the scenes, much like Subutai’s strategic planning and execution of campaigns. Subutai’s role was crucial to the Mongol conquests, just as Lp(a)’s contribution to cardiovascular risk is significant, though less recognized than that of LDL-C.

The Allegory

Genghis Khan’s reliance on Subutai’s strategic genius mirrors the dangerous partnership between LDL-C and Lp(a) in elevating cardiovascular risk. While Khan’s (LDL-C’s) conquests are well-documented and visible, Subutai’s (Lp(a)’s) contributions, though less known, were vital to the success of those campaigns. This highlights the importance of recognising both the well-known and the less visible factors in CVD. Just as Subutai’s strategies were key to the Mongol Empire’s expansion, Lp(a)’s role in cardiovascular health is critical and warrants greater attention for a comprehensive risk assessment.

Like LDL-C, Lp(a) is composed of a core of fats, including cholesterol esters and triglycerides, wrapped in a layer that includes phospholipids and free cholesterol, along with a protein called apoB-100. The key thing that sets Lp(a) apart from other types of LDL is an extra protein called apo(a)2.

Lp(a) is thought to contribute to CVD risk through several mechanisms. Firstly, Lp(a) molecules display all the same atherosclerotic risk as LDL-C molecules due to their similar fundamental composition5. However, Lp(a) is particularly good at clogging arteries, more so than the other types of cholesterol because of its apo(a) molecule. This part makes it harder for your body to break down blood clots. Apo(a) looks a lot like plasminogen, another substance in your body that usually helps dissolve clots. Because they look so similar, apo(a) ends up taking the place of the helpful substance on the spots where it works, meaning your body is less able to dissolve clots. This can lead to more clogging in your arteries5.

Lp(a) is believed to be particularly good at carrying harmful substances called oxidized phospholipids (OxPLs) which stick to apo(a). This combination can increase inflammation in the body by boosting the production of inflammatory proteins and stimulating the release of molecules that attract immune cells, making it easier for Lp(a) to get into the walls of blood vessels5. While more research is needed to fully understand these processes, studies suggest that Lp(a) can interfere with the body’s ability to break down blood clots in a roundabout way6. This interference is thought to be one of the reasons Lp(a) contributes to the risk of forming unwanted clots, making it particularly dangerous for heart health5.

It’s always the little ones.

Your Lp(a) levels are entirely dependent on your genetics. Everyone has two versions of the apo(a) protein, one inherited from each parent, and these versions can be different from each other7. The differences between these versions depend on how many times a certain section, called KIV2, is repeated in the protein’s structure. Some versions of apo(a) have fewer repeats making them smaller in size7. These smaller versions are made more quickly by the body and end up being more abundant in the bloodstream than the larger versions8. The size and quantity of these particles are critical factors in assessing heart disease risk.

Smaller Lp(a) particles are of particular concern and thought to contribute more to CVD risk7 potentially due to their efficiency in contributing to the buildup of plaques within arteries. These plaques are central to the development of atherosclerosis4. The increased concentration of smaller Lp(a) particles may enhance their potential to penetrate arterial walls, deposit cholesterol, and accelerate plaque formation.

This process highlights why it’s key to know your own Lp(a) type, as differences in the apo(a) protein affect both how much Lp(a) you have in your blood and your chance of heart disease.

As your genes have a big say in your Lp(a) levels there isn’t anything you can do to lower your Lp(a) levels. Just like there wasn’t much anyone could do to stop Subutai. However, if you stop Khan and his armies, Subutai becomes much less effective. Similarly, by lowering the other factors that contribute to your CVD risk, like LDL-C, you can lower your overall risk. Essentially, by developing healthy diet and lifestyle habits you can help reduce the numbers of the cholesterol armies at the gates. However, its important to know how many loyal Lp(a) soldiers

Lp(a) Testing

At Randox Health, we believe its important to know your underlying risk of CVD so that, if necessary, you can make the changes you need to have the wellbeing you deserve. In our comprehensive Signature packages we include Lp(a) testing along with other known cardiac risk markers to ensure you get the full picture of your heart health.

To learn more about these comprehensive health test packages, visit our website, or get in touch with us today by clicking here.

Open Reference ListClose Reference List:

1. World Heart Federation. World Heart Report 2023 Confronting the World’s Number One Killer.; 2023.

2. Stürzebecher PE, Schorr JJ, Klebs SHG, Laufs U. Trends and consequences of lipoprotein(a) testing: Cross-sectional and longitudinal health insurance claims database analyses. Atherosclerosis. 2023;367:24-33. doi:10.1016/j.atherosclerosis.2023.01.014

3. Scheel P, Meyer J, Blumenthal R, Martin S. Lipoprotein(a) in Clinical Practice. Latest in Cardiology. Published online July 2, 2019. Accessed March 22, 2024. https://www.acc.org/Latest-in-Cardiology/Articles/2019/07/02/08/05/Lipoproteina-in-Clinical-Practice

4. Pahwa R, Jialal I. Atherosclerosis.; 2024.

5. Tsimikas S. A Test in Context: Lipoprotein(a). J Am Coll Cardiol. 2017;69(6):692-711. doi:10.1016/j.jacc.2016.11.042

6. Boffa MB, Koschinsky ML. Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease? J Lipid Res. 2016;57(5):745-757. doi:10.1194/jlr.R060582

7. Schmidt K, Noureen A, Kronenberg F, Utermann G. Structure, function, and genetics of lipoprotein (a). J Lipid Res. 2016;57(8):1339-1359. doi:10.1194/jlr.R067314

8. Kronenberg F, Mora S, Stroes ESG, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43(39):3925-3946. doi:10.1093/eurheartj/ehac361