Researchers have warned about high levels of Lipoprotein(a), a silent killer disease that impacts one in five people globally and for which there is currently no cure.

High levels of Lipoprotein(a), known as Lp(a), a largely genetic form of cholesterol, can lead to heart attacks and strokes and currently because it is genetic, rather than lifestyle based – there is no treatment. With no approved treatment currently on the market, Lp(a) plays a part in millions of deaths every year.

High lipoprotein (a)

Lipoprotein (a) is a lot like LDL cholesterol (sometimes called ‘bad cholesterol’) but it’s more ‘sticky’. If you have high levels of lipoprotein (a) in your blood, it can stick to your artery walls and clog them up, leading to heart disease and stroke at a young age.

Lipoprotein (a) is also known as Lp(a) for short. It’s passed on in your genes.

What is Lp(a)?

Lp(a) is a large lipoprotein made by the liver. Lipoproteins are parcels made of fat and protein. Their job is to carry fats (also called lipids) around the body in the blood. LDL cholesterol (or ‘bad cholesterol’) is also a lipoprotein.

Lp(a) is made of:

– a lipoprotein similar to LDL cholesterol (bad cholesterol)

– plus two proteins known as ApoB and Apo(a).

Apo(a) is very sticky. It’s thought to be involved in the blood’s clotting system. When Apo(a) is added to a lipoprotein, it can be likened to adding a patch of Velcro to normal LDL cholesterol.

A high level of Lp(a) in the blood has now been identified as a risk factor for diseases of the heart and blood vessels – known as cardiovascular disease or CVD. It can cause atherosclerosis (furring up of arteries), heart attacks, strokes, aortic valve disease and heart failure.

How does high Lp(a) lead to disease?

1) Lp(a) is thought to speed up the narrowing of the arteries because it is held in the artery walls more readily than LDL cholesterol due to the “sticky” Apo(a).

2) It is thought to increase the development of blood clots.

What causes high Lp(a)?

The amount of Lp(a) in your blood is determined by your genes.

Ethnic background might make a difference: Lp(a) levels have been found to be lower in some populations including Chinese and Japanese, and higher in others including African populations.

Lp(a) levels are not affected by your age or sex.

There are also ‘secondary causes’ that can affect your Lp(a) levels. These include conditions such as chronic kidney disease (CKD), nephrotic kidney disease and hypothyroidism.

How is high Lp(a) diagnosed?

Lp(a) is not routinely measured in general practice when you have a cholesterol test. In the UK, it can be measured by a specialist lipid clinic. Your GP can send an advice and guidance referral for testing via a lipid clinic if you have:

• premature CVD, or there is premature CVD in your family
• a family history of high Lp(a)
• familial hypercholesterolaemia (FH)
• calcific aortic valve disease
• a borderline (but <15%) 10 year risk of CVD.

Because your Lp(a) levels are mainly determined by your genes, family screening is important.

Lp(a) can be measured in a number of different ways, such as mass (mg/dL or mg/L) or particle numbers (nmol/L). It is important to find out what unit your Lp (a) has been measured in.

If you have your Lp(a) level measured, your specialist will be able to talk to you about what your results mean in terms of your overall risk of disease (low, moderate, high or very high risk).

How is high Lp (a) treated?

Managing other risk factors

At the moment, the most important way to manage high Lp(a) is optimising the treatment of all other risk factors for heart disease, particularly non-HDL cholesterol. This is all your cholesterol that is not HDL (sometimes known as ‘good’ cholesterol) most of which is LDL cholesterol (known as bad cholesterol).

Diagnosing and treating other diseases

As other conditions can affect your Lp(a) level, such as chronic kidney disease (CKD), nephrotic kidney disease and hypothyroidism, your GP should aim to find out if you have any underlying conditions and begin treatment.

Keeping an eye on your overall health

Because Lp(a) levels are determined by your genes, they do not change throughout your lifetime. They are usually unaffected by your diet, lifestyle or environment. This means once you’ve had your Lp(a) level measured, you won’t usually need to have it checked again.

However, it is important to be aware of other things that can raise the risk of heart disease – such as being overweight, raised blood pressure, not being physically active, a diet high in saturated fat, smoking and drinking too much alcohol – and make healthy changes.

Eating a healthy diet
At the moment there is not enough evidence to know whether making changes to your diet can make a meaningful difference to your Lp(a) levels, but it can lower your LDL (bad cholesterol) as well as other types of cholesterol and risk factors for heart disease, such as your blood pressure. Eat a healthy diet to lower your risk of heart disease overall.

Rather than focusing on individual foods, go for a healthy, balanced diet and maintain a healthy weight. For example:

• cut down on foods high in saturated fat
• and replace these with foods rich in healthy unsaturated fats
• eat plenty of fruit and vegetables – at least 5 a day
• choose wholegrain starchy foods like brown rice, wholemeal bread or wholemeal pasta
• eat two portions of fish per week, one of which is oily (such as mackerel, sardines, salmon)
• eat vegetable sources of protein more often, such as pulses, beans, lentils, soya and nuts
• avoid sugary foods with added sugars and sweetened drinks
• if you drink alcohol, drink only in moderation
• include foods which are known to lower cholesterol, such as oats and foods fortified with plant stanols and sterols

Statins

It is also recommended that you take a medication such as a statin. Statins do not lower the amount of Lp(a) but they will shrink the size of the Lp (a) lipoproteins. They will also lower non-HDL cholesterol levels.

Our consensus statement recommends that management of high Lp(a) should include:

1. reducing your overall risk of heart disease and stroke

2. aiming for a non-HDL cholesterol level of below 2.5mmol/L for those seen as high risk.

New treatments being researched

Currently there are new treatments being researched in clinical trials which stop Lp(a) being made at genetic level:

• one is known as an antisense “oligonucleotide” therapy
• the other is known as small interfering or siRNA (gene silencing) treatment.

Recent results reported in early 2022 have shown a reduction in Lp(a) levels of between 46% and 98%. However, research is still needed to find out whether treatments that lower Lp(a) levels help prevent heart disease and strokes.

Other treatments

Other treatments shown to help lower Lp(a) levels include:

• PCSK9 inhibitors These reduce levels by 20-30%, but they are not currently licenced for lowering Lp(a).
• Lipoprotein apheresis. This is a weekly-fortnightly treatment similar to renal dialysis which can reduce Lp(a) levels by up to 75%. This treatment should only be considered in people with recurrent CVD despite optimal control of other risk factors.