Lipoprotein a (Lp(a))

Introduction to Lipoprotein a

Lp(a) is a type of fat that has a similar structure to low-density lipoprotein (LDL) cholesterol, but is ‘stickier’. That’s because it has a lipid (fat) rich core surrounded by two proteins, apolipoprotein B-100 and apolipoprotein A^[1].

High levels of Lp(a) are a risk factor for heart disease because Lp(a) can make it easier for blood clots to form in your blood and for plaque to build up in your artery walls, contributing to atherosclerosis and heart disease.

Why is Lp(a) Important?

Lipoprotein a is a well known and genetically determined risk factor for several heart related conditions, including:

• atherosclerosis

• coronary artery disease

• blood clots (thrombosis)

• narrowing of the aortic valve (aortic stenosis)^[2]

It is estimated that between 20% and 25% of the world’s population have Lp(a) levels of 50 mg/dL or more, a figure that’s associated with an increased cardiovascular risk^[3].

An increase in Lp(a) levels of 100 nmol/L is associated with an 8% higher risk of a second major adverse cardiovascular event and more than an 18% increased risk of coronary revascularisation in people with atherosclerotic cardiovascular disease (ASCVD) who had already experienced a major heart event, such as a heart attack^[4].

Elevated Lp(a) levels contribute to heart disease through several mechanisms associated with increased development of fatty plaques in artery walls (atherogenesis), inflammation, and thrombosis^[5], but levels are largely determined by your genes^[6], they are not affected by your sex or age.

Lp(a) levels are 75 to 95% heritable which means they are almost entirely determined by your genetic makeup^[7]. So, Lp(a) levels are usually tested in families where one member has high levels because of the increased risk of heart disease and stroke.

Your ethnic background can increase your Lp(a) levels. For example, people of African descent have the highest Lp(a) levels compared to other ethnicities^[8][9]. Another risk factor for elevated Lp(a) levels is familial hypercholesterolemia, an inherited condition that causes high blood LDL cholesterol levels^[10], especially if you already have cardiovascular disease^[11].

How is Lp(a) Measured?

The only way to find out your Lp(a) level is through a blood test. It doesn’t form part of a standard lipid panel or blood fat test. You can measure your Lp(a) levels at home with our finger prick blood test.

It’s important to check your Lp(a) levels at least once because, unlike other types of cholesterol whose levels can fluctuate because of diet, exercise, medication, and so on, Lp(a) levels are mostly determined by your genes, remain relatively constant over your lifetime^[12], and are largely unaffected by lifestyle or cholesterol-lowering therapies, like statins.

Like high LDL cholesterol levels, you’re unlikely to have any signs or symptoms indicating that your Lp(a) levels are high. However, you may be at an increased risk if you:

• have a family history of heart disease

• at least one relative has high Lp(a) levels

• are of black ethnicity

What Do Lp(a) Results Mean?

High Lp(a) levels increase your risk for developing coronary artery disease and cerebral vascular disease, especially if you also have high cholesterol levels. However, you can have high Lp(a) levels and normal or low LDL cholesterol levels in the blood^[13].

The cardiovascular risk associated with Lp(a) levels depend on the Lp(a) level. In other words, the higher the Lp(a) level in your blood, the higher your risk of heart disease. This is shown in the table below:

When Lp(a) levels are high, it can stick to your blood vessel walls, forming plaques, and causing your arteries to narrow, a condition called atherosclerosis. Although LDL cholesterol does the same when it is high, Lp(a) is more damaging and more likely to cause blockages and blood clots^[14].

High Lp(a) levels are associated with an increased risk of:

• heart attacks

• stroke

• heart disease

• heart failure

• peripheral artery disease

• narrowing of the aortic valve (stenosis)

The earlier you understand your Lp(a) levels, the earlier you can take positive action to reduce your risk of cardiovascular disease.

Low Lp(a) levels are not usually a cause for concern, but some emerging research suggests that very low levels may be linked to higher risks of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD)^[15].

Can Lp(a) Levels Be Managed?

Because Lp(a) levels are mostly determined by your genes, lifestyle modifications and medical interventions will only have a limited effect. However, these changes and transitioning to a healthier lifestyle can reduce your overall risk of developing heart disease and have a positive impact on other risk factors.

Some of the ways you can bring down your cardiovascular risk, include:

• Eating a heart-healthy diet

  following diets that promote the consumption of healthy fats, like omega-3s and mono- and polyunsaturated types, fruit, vegetables, fish, and a limited consumption of meat, like the Mediterranean Diet can have a profound impact on your heart disease risk. Some research shows that the Mediterranean diet can reduce Lp(a) levels by 50% in women with metabolic syndrome after 12 weeks^[16]. While a further study investigating the effects of a polyunsaturated fatty acid (PUFA) enriched diet found that it could reduce Lp(a) levels by around 11% over six weeks^[17].

• Regular exercise

  although exercise will have little effect on Lp(a) levels specifically, regular aerobic exercise can be beneficial for keeping atherosclerosis at bay, by lowering lipid levels in your blood like, LDL cholesterol and triglycerides. It also lowers your blood pressure and controls your weight, both of which are risk factors for developing heart disease^[18].

• Quitting smoking

  smoking is a big risk factor for coronary heart disease^[19] and causes almost 20,000 heart-related deaths in the UK every year^[20]. When you give up smoking, your risk of a heart attack is halved compared to a smoker’s^[21] and after 5 years your risk of cardiovascular disease is significantly lower^[22].

• Keeping stress under control

  mental stress is an emerging risk factor for the development of coronary artery disease and stroke because it increases inflammation, promoting the buildup of plaque in the arteries^[23]. Some studies have shown that completing just 15 minutes of meditation per day can reduce the risk of stress-related heart attacks, strokes, and deaths by as much as 48%^[24].

• Consider cholesterol-lowering medication

  if you have elevated LDL cholesterol levels that are not coming down with lifestyle changes alone, you may need to consider statins. These lower the amount of LDL being produced by your liver which reduces the amount in circulation, lowering the risk of atherosclerosis and other heart related complications. However, some research suggests that statins may increase Lp(a) levels^[25] by 10 to 20%^[26] in some people, so it is important to discuss your options with your doctor following a high Lp(a) result.

One of the biggest challenges in recognising Lp(a) as a major cardiovascular risk factor has been the lack of effective treatments available to lower its levels. Although clinical trials testing Lp(a)-lowering treatments are highly anticipated, some medications have already had some therapeutic benefit. The table below outlines some of the therapeutic management strategies for people with high Lp(a) levels.