Lipoproteina the bad guy of lipidology hdr

Lipoprotein(a) - the bad guy of lipids

In a previous blog, I tried to explain how dyslipidaemia (abnormal levels of blood lipids) causes atherosclerosis (plaques forming in the arteries) using the analogy of a stag-do. In this blog, I’m going to stretch this analogy even further. 

In the stag do analogy, low-density lipoprotein (LDL) particles are members of the stag do. This is because it is LDL that causes all the trouble in the wall of the artery. In the same way, stag-dos cause trouble in bars the world over. The way to think of lipoprotein(a) is as the really bad, malevolent guy on a stag do. The guy with an evil streak that everyone else is a little bit wary of. 

Lipoprotein (a) is a type of LDL particle. It is made up of a glycoprotein (a sugar linked to a protein), an apolipoprotein B molecule that is linked to an apolipoprotein (a). 

Lipoprotein (a) isn’t all bad. It does have an important role in acute inflammation and wound healing. In our stag-do analogy, our protagonist can be thought of as a guy who is edgy, who brings a sense of excitement, a certain frisson. But this guy is one of those people who are best in small doses. On a stag-do, this bad dude is the type of person who would buy the stag 8 shots of gin to render him comatose, cheat on his partner, start a fight in a bar and get everyone kicked out. In the body, lipoprotein (a) causes problems by:

  • Interfering with the breakdown of clots.
  • Interfering with the functioning of the lining of the artery. 
  • Increasing inflammation in the wall of the artery.
  • Accelerating the formation of foam cells which leads to atherosclerotic plaque formation. 

The main determinant of our levels of lipoprotein (a) is our genes. Levels can be measured using a standard blood test. Unfortunately, Lp(a) is not routinely measured on standard blood tests. Generally, the levels of Lp(a) remain stable over time although they can be affected to some extent by reduced levels of oestrogen and due to inflammation. 

High levels of Lp(a) are associated with increased risk of heart and vascular disease as well as narrowing of the aorta. People who have a condition known as Familial Hypercholesterolaemia have a higher likelihood of having high levels of Lp(a). In these people, high Lp(a) further increases their already high risk of developing cardiovascular disease. 

The European Society of Cardiology recommends that everyone should have their levels of Lp(a) checked at least once in their lifetime. Certainly, the following groups of people should have their Lp(a) levels checked:

  • Those with premature cardiovascular disease. 
  • People with a family history of premature cardiovascular disease (<55 years of age in men and <65 years of age in women).
  • People with a family history of elevated Lp(a).
  • People with a history of Familial Hypercholesterolaemia. 
  • People with a history of recurrent cardiovascular disease despite optimum treatment. 

In addition, Lp(a) measurement can be useful for people with borderline cardiovascular risk scores who doctors are considering treatment with a statin and in people whose LDL cholesterol has not lowered as expected despite statin treatment. 

So what can be done with elevated levels of Lp(a)? Currently, there is only limited scientific evidence to suggest that lowing Lp(a) reduced the risk of heart and vascular disease. Therefore, our focus of treatment is to reduce other risk factors for heart disease as much as possible. This includes lowering the levels of LDL as much as possible, usually with one or more medications. These medications include statins and another cholesterol-lowering medication called ezetimibe. 

For some people, it is not possible to achieve optimum levels of LDL even with a statin at the maximum tolerated dose and ezetimibe, another cholesterol-lowering drug. For these patients, a medication called a PCSK9 inhibitor is required. These medications have been shown to reduce Lp(a) in some people and reduce the risk of heart disease independent of levels of LDL.  

Some doctors use Nicotinic acid to reduce Lp(a). This medication has side effects that make it difficult to tolerate. Medical studies have shown that it does reduce Lp(a). However, these studies have not demonstrated that Nicotinic acid reduces the risk of heart disease. Another treatment called apheresis can reduce levels of Lp(a) temporarily but it is not clear yet whether this reduces the risk of heart disease. 

A new promising therapy for elevated Lp(a) is antisense therapy. This is a type of gene therapy that intercepts the message from the body’s genetic code to make one of the key components of Lp(a). Trials in this treatment are ongoing. 

Although there is no really effective current treatment to lower Lp(a) it is still very worth having levels checked at some stage of your life. Knowing your Lp(a) means that if they are elevated you can take steps that significantly reduce your risk of heart disease. 

Dr Hugh Coyne

Private GP

Parsons Green